睡眠剥夺与动脉粥样硬化病变的相关性研究
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摘要
睡眠剥夺(sleep deprivation, SD)一词起源于对持续/连续工作状态导致的睡眠缺失的描述,后逐渐发展成为一个独立的概念,具体指人因环境或自身原因丧失了所需要睡眠量的一种过程和状态。一般24小时内的睡眠少于6-8小时则认为发生了睡眠剥夺。随着现代生活节奏的加快以及社会竞争的加剧,SD成为一个非常重要的社会问题。另外在某些职业或人群,SD不可避免。常有持续工作,睡眠不足而诱发心脏病的报道,更有甚者可导致猝死。
SD影响了机体固有的生物节律,使机体处于应激状态。应激是机体对各种有害刺激的反应。应激早期机体出现保护防御性的快速动员并处于最佳状态,但持续时间短,随后机体进入抵抗或适应阶段,持续强烈的有害刺激将耗竭机体的抵抗能力,机体内环境明显失衡,应激反应的负效应陆续显现,出现应激相关的疾病、器官功能衰退甚至体克、死亡。
机体受到强烈刺激时,应激反应的神经内分泌改变为蓝斑-去甲肾上腺素能神经元／交感-肾上腺髓质轴和下丘脑-垂体-肾上腺皮质轴(hypothalamus-pituitary-adrenal, HPA)的强烈兴奋。参与应激反应最重要的是HPA轴。HPA轴激活,促进促肾上腺皮质激素释放激素释放,进而刺激促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)的分泌,增加皮质醇(cortisol, CORT)的分泌,HPA轴的活动受到体内外各种应激性刺激的影响而发生改变。ACTH水平直接反映HPA轴的功能状态。CORT是HPA轴的终末产物,对机体的糖、脂肪和蛋白质的代谢有重要影响,因此常作为研究应激的最经典、最重要的指标之一。CORT能直接影响糖、蛋白质、脂肪等三大营养物质代谢,还有抑制免疫作用,增加了心血管系统对儿茶酚胺和其它加压物质的反应性,加强去甲肾上腺素对动脉的收缩作用,促进肝脏生成血管紧张素原,使肾素与之结合而转化为血管紧张素。引起Na+、H2O潴留,增加血容量,引起血压升高。引起白细胞增多,增加氧自由基的产生。而氧自由基损害血管内皮细胞的结构和功能,内皮细胞通透性增加,脂质易于侵入血管内膜,促进AS的发生和发展。近期也有研究提示冠心病的发生发展过程与HPA轴有着密切的关系。
氧化应激是指机体内抗氧化物和氧化物生成系统之间的不平衡。生物体进行有氧代谢时可产生活性氧。正常情况下,体内氧自由基的产生和清除是平衡的,当自由基产生过多或体内抗氧化物相对不足时,体内氧自由基代谢就会出现失衡,自由基在体内累积过多,就会攻击机体,即发生氧化应激。SD可通过多种途径诱发机体的氧化应激。具体包括SD后导致能量消耗代谢及自由基的增多,机体抗氧化能力降低以及通过内质网应激间接引起氧化应激三条途径。氧化应激条件下,儿茶酚胺和糖皮质激素升高,以动员机体各方面的机制来对付应激作用下机体出现自由基产生和清除失衡。自由基在体内大量“堆积”,引发广泛的损伤效应。
动脉粥样硬化(atherosclerosis, AS)是严重危害公众健康的常见病和多发病,近年在我国呈增长趋势。AS是一种发生在大中动脉的疾病,如冠状动脉、颈动脉、四肢末端的动脉和弹性动脉(如主动脉、髂动脉)。粥样斑块可堵塞动脉管腔,且极易发生血栓、出血、栓塞和动脉破裂等,导致严重的后果。目前认为,AS的发生及发展与炎症反应有关。最近研究指出：AS实质上是一种复杂、缓慢进展的炎症过程。炎性反应在AS的发生、发展及最后斑块表面破裂并发血栓形成的所有阶段均具有重要作用。目前有较多关于SD影响炎症因子释放的报道表明SD可促发应激反应而导致各类炎性蛋白释放。而这些炎性蛋白又可危及心血管系统。
近年来,越来越多的证据显示对于急性心脑缺血性临床事件的发生,不稳定AS斑块是较动脉狭窄更危险的因素。急性冠脉综合征的发生常与一些不稳定斑块及继发血栓密切相关,这些斑块常常并不导致严重的管腔狭窄,却容易发生破裂、糜烂、钙化等情况而易于继发血栓导致临床高危事件的发生。在AS损伤中,富含脂质的巨噬泡沫细胞聚集是易破斑块的重要特征,巨噬细胞分泌基质金属蛋白酶(matrix metalloproteinases, MMPs)在斑块破裂中起重要作用。MMPs几乎能降解细胞外基质的所有成分,削弱纤维帽对斑块的保护作用从而促进斑块的破裂。MMPs目前被认为是动脉粥样硬化和冠心病的独立危险因素。MMP-9是MMPs家族中的重要成员,在AS斑块处的血管重构、斑块的不稳定及其破裂诱发的急性冠脉综合征都扮演着重要的角色。
本研究对AS大鼠采用“改良多平台睡眠剥夺法”建立SD模型,分别对其进行1、3、5、7天SD。SD后检测各组AS大鼠血清中及主动脉组织内神经内分泌功能改变、氧化应激、炎症反应的相关指标变化趋势,并以主动脉组织内MMP-9蛋白表达水平作为评价斑块稳定性的指标,同时结合观察SD后各组大鼠的生理、行为改变,心电图变化,主动脉组织形态学改变,以探讨SD后的AS大鼠主动脉组织本身是否因为SD所致的神经内分泌功能改变、氧化应激、炎症反应等而受到损伤,促进斑块的发展、破裂从而导致急性心脑血管事件的发生。
第一章睡眠剥夺对动脉粥样硬化大鼠神经内分泌功能变化的影响
目的：
以神经内分泌系统所产生的两种与心血管疾病密切相关的激素,ACTH及CORT为切入点,通过测定其在血清中的表达量在不同SD时间情况下的波动情况,分析HPA轴功能状态,来反映SD对大鼠神经内分泌功能变化的影响。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、观察SD后AS大鼠的生理及行为改变。
(四)、检测SD后AS大鼠血清ACTH及CORT含量。
结果：
(一)、SD后AS大鼠精神状态逐渐转差,反应变迟钝,食欲不振,身体渐消瘦、变虚弱,皮毛变粗糙、蓬乱而没有光泽。且随着SD时间的延长,AS大鼠呈先兴奋,然后激惹,最后衰竭的变化趋势。
(二)、SD后AS大鼠ACTH及CORT水平呈先增高后下降的波动性变化。
结论：
SD造成的应激性刺激,能够激活HPA轴,并刺激与心血管危险因素密切相关的ACTH及CORT分泌,且随着SD时间的变化,激素分泌水平发生波动,并反馈性地引起应激水平的变化。从而对心血管系统产生影响,促进AS大鼠的AS进展。
第二章睡眠剥夺对动脉粥样硬化大鼠氧化应激水平的影响
目的：
以还原型谷胱甘肽(glutathione, GSH)、脂质过氧化物丙二醛(malondialdehyde, MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)及超氧化物歧化酶(superoxide dismutase, SOD),四种氧化应激的重要指标为代表,观察SD情况下,AS大鼠主动脉组织的氧化应激水平及其变化趋势,了解SD所致的氧化应激对AS大鼠AS病变进程的影响。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、检测SD后AS大鼠主动脉组织GSH及MDA含量。
(四)、检测SD后AS大鼠主动脉组织GSH-Px及SOD活性。
(五)、作各指标与SD时间间的相关性分析。
结果：
(一)、SD后AS大鼠主动脉组织GSH含量降低,且随着SD时间的延长,其含量呈现逐渐降低的趋势。
(二)、SD后AS大鼠主动脉组织GSH-Px活性降低,且随着SD时间的延长其活性呈现逐渐降低的趋势。
(三)、在SDld AS大鼠主动脉组织SOD活性水平明显升高并达到最高值,而后随着SD时间的延长,SOD活性水平降低,呈持续下降趋势。
(四)、SD后AS大鼠主动脉组织MDA含量升高,且随着SD时间的延长,其含量呈现逐渐升高趋势。
(五)、GSH、GSH-Px、SOD与SD时间呈负相关关系(r=-0.949,-0.977,-0.590,P<0.001)。MDA与SD时间呈正相关关系(r=0.984,P<0.001)。
结论：
SD后,AS大鼠发生氧化应激反应,且随着SD时间的延长,机体的抗氧化能力逐渐减弱,所受氧化损伤逐渐加重,从而加速AS病变进程的发展。
第三章睡眠剥夺对动脉粥样硬化大鼠致炎因子水平的影响
目的：
以经过不同时长SD后的AS大鼠血清及主动脉组织为样本,检测随SD时间变化,AS大鼠血清中TNF-α、hs-CRP、IL-6水平及主动脉组织中NF-κB蛋白表达水平的变化情况,以期了解SD是否可以引起AS大鼠机体发生炎症反应,及其反应程度随SD时间的变化趋势,以探讨SD是否可以通过激活炎症反应而促进AS进程的发展。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、检测SD后AS大鼠血清TNF-α、hs-CRP、IL-6水平。
(四)、检测SD后AS大鼠主动脉组织NF-κB蛋白表达水平。
(五)、作各指标与SD时间间的相关性分析。
结果：
(一)、SD后AS大鼠血清中的TNF-α水平升高,且随着SD时间的延长,其水平呈现逐渐升高的趋势。
(二)、SD后AS大鼠血清中的hs-CRP水平上升,且随着SD时间的延长,其水平呈现持续上升的趋势。
(三)、SD后AS大鼠血清中的IL-6水平升高,且随着SD时间的延长,其水平逐渐升高。
(四)、SD后AS大鼠主动脉组织NF-κB蛋白表达水平随着SD时间的延长呈逐渐升高的趋势。
(五)、TNF-α、hs-CRP、IL-6、NF-κB与SD时间均呈正相关关系(r=0.952,0.951,0.961,0.986,P<0.001)。
结论：
SD后,AS大鼠炎症反应激活,且随着SD时间的延长,机体的炎症反应持续发展,主动脉组织AS病变加重。SD可通过激活炎症反应而促进AS病变进程的发展。
第四章睡眠剥夺对动脉粥样硬化大鼠斑块稳定性的影响
目的：
以SD后的AS模型大鼠为研究对象,观察其心电图表现,利用光镜观察其主动脉形态学改变,通过检测其主动脉组织内MMP-9蛋白表达水平作为评价斑块稳定性的指标,以了解随着不同SD时间,上述各项的变化,探讨SD是否促进AS斑块的不稳定,从而促进了AS病变的进程。并用多元逐步回归方法分析前述有关神经内分泌、氧化应激、炎症相关指标中对MMP-9蛋白表达水平有影响的指标,以明确SD是否从神经内分泌、氧化应激、炎症三方面对AS大鼠产生影响,从而促进其AS斑块的不稳定、破裂,加重AS病变的发展。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、SD后AS大鼠心电图监测。
(四)、SD后AS大鼠主动脉组织光镜标本制备及观察。
(五)、SD后大鼠主动脉组织MMP-9蛋白表达水平检测。
(六)、作各指标与SD时间间的相关性分析。
(七)、用多元逐步回归方法分析前述有关神经内分泌、氧化应激、炎症相关指标中对MMP-9蛋白表达水平有影响的指标。
结果：
(一)、SD后AS大鼠心率变化较大。随着SD的时间延长,AS大鼠心率呈先增快后减慢的波动性变化。
(二)、随着SD的时间延长,AS大鼠心电图ST-T逐渐上抬,T波高耸直立,显示SD引起心肌全层缺血。
(三)、SD后AS大鼠主动脉AS病变程度随着SD时间的延长而逐渐加重。
(四)、SD后AS大鼠主动脉组织MMP-9蛋白表达水平升高,且随着SD时间的延长,其表达水平呈持续升高的趋势。
(五)、心电图ST-T改变、MMP-9与SD时间呈正相关关系(r=0.883,0.978,P<0.001)。
(六)、通过多元逐步回归分析发现影响AS大鼠主动脉组织MMP-9蛋白表达水平的主要因素为：ACTH、MDA、hs-CRP及IL-6。
结论：
SD可使AS大鼠分别在神经内分泌、氧化应激以及炎症三个方面发生变化,从而导致AS大鼠主动脉组织MMP-9蛋白水平发生改变,从而促进其AS斑块的不稳定、破裂,加重AS病变的发展。
The concept of sleep deprivation (SD) originated in the continuing/continuous working state lead to lack of sleep. It describes a process and status that person loss of the required amount of sleep because of the environment or himsely reasons. Generally, sleep less than6-8hours within24hours, means it take place SD. With the accelerated pace of modern life and social competition, SD become a very important social issue. SD in some occupations or groups is inevitable. We often heard of some reports of heart attack or sudden death at worse due to continuing working and insufficient sleep.
SD can influence the body inherent biological rhythm, so that the body was in stress state. Stress is the body reaction for various kinds of harmful stimulation. The body will occur rapid mobilization of defensive protection and at its best state in early period of stress. However, t he duration is short. Then the body state is going into the resistance or adaptation stage. Noxious stimulation is continuing strongly deplete to the body's resistance. At that time, the internal environment is significantly imbalanced. The negative effects of stress including stress-related diseases, organ function decline, even shock and death have become more obviously.
When body was strongly stimulated, the changes of the neuroendocrine response to stress were the strongly excited of locus coeruleus-norepinephrine neurons/sympathetic-adrenal axis and hypothalamus-pituitary-adrenal (HP A) axis. The role of HPA axis involved in stress response is the most important. When HPA axis was activated, it can accelerate the release of corticotropin releasing hormone, thereby, stimulating the secretion of adrenocorticotropic hormone (ACTH), increased cortisol (CORT) secretion,. Activity of HPA axis can be changed affected by various stress stimuli in vivo and vitro. The levels of ACTH directly reflect the state of HPA axis function. CORT is the end products of HPA axis. It has important implication for glucose, fat and protein metabolism of body. Therefore, it is considered as one of the most classic and important indicators in stress research. CORT can directly affect glucose, protein and fat metabolism, suppress immune function, increased the reactivity of cardiovascular system on catecholamine and other pressurized reactive substances. It also can strengthen of norepinephrine on contraction of the artery, accelerate the liver produce angiotensinogen. It can combine with renin into renin-angiotensin. It caused Na+, H2O retention, increased blood volume, elevated blood pressure. It can induce leukocytosis, increase the production of oxygen free radicals. The oxygen free radical can damage to structure and function of vascular endothelial cells. When the permeability of endothelial cells Increased, it lead lipid can easily invade intima, then the occurrence and development of AS is accelerated. Recent researches have reported that occur and development process of coronary heart disease is closely related to HPA axis.
Oxidative stress means imbalance between body antioxidants and the oxide generating system. Organisms can produce reactive oxygen species when they are doing for aerobic metabolism. Under normal circumstances, the production and clear of oxygen free radicals in vivo is balanced. When too many free radicals or antioxidants in vivo relatively low, free radicals in the body will imbalance. When the accumulation of free radicals in the body is excessively, it will attack the body, that is, oxidative stress. SD can induce oxidative stress by a variety of ways. Three ways, specifically including the cause of energy metabolism and expenditure and the increase in free radicals after SD, reduced antioxidant capacity as well as through the endoplasmic reticulum stress induced oxidative stress indirectly. In oxidative stress conditions, elevated catecholamine and glucocorticoid can mobilize the body in all aspects of the mechanism to cope with the free radical generation and scavenging imbalance occur in the body. A large number of free radicals accumulation in the body, then they caused extensive damage.
Atherosclerosis (AS) is a common and frequently-occurring disease, it is seriously harm to public health. In recent years, AS has an increasing trend in China. AS is a disease in large and medium arteries, such as coronary, carotid arteries, the arteries of the extremities and elastic arteries (e.g. aorta, iliac arteries), arterial lumen can be blocked by Atherosclerotic plaques. As is a disease prone to blood clots, bleeding, thrombosis and arterial rupture, it can lead to serious consequences. Currently considered that the occurrence and development of AS is related to inflammatory reaction. Recent studies have pointed out that AS is essentially a complex, slow progress of the inflammatory process. Inflammation is playing an important role in all stages of AS, including the occurrence and development of AS, plaque surface rupture and finally complicated with thrombosis. There are more reports about SD affects the release of inflammatory cytokines, indicate that SD can trigger the stress response which led to the release of various inflammatory protein. These inflammatory proteins can also endanger the cardiovascular system.
In recent years, more and more evidence of acute cerebral and cardiac ischemia clinical events, indicated that AS unstable plaques is a more dangerous factor than arterial stenosis. The occurrence of acute coronary syndrome is often closely related to some unstable plaques and secondary thrombosis. These patches often do not lead to severe stenosis, it prone to rupture, erosion, calcification, etc. and easily to secondary thrombosis, lead to the clinical high risk events. Accumulation of lipid-rich macrophage foam cells in AS Injury is an important feature of plaque easy to break. Macrophages secrete matrix metalloproteinase (MMPs), witch play an important role in plaque rupture. MMPs are now thought as an independent risk factor of atherosclerosis and coronary heart disease, MMP-9is an important member of the family of MMPs. MMP-9plays an important role in vascular remodeling in AS plaque, unstable plaque and its rupture induced acute coronary syndrome.
In this study, we used "modified multiple platform method of SD" to establish SD model with AS rats. After1,3,5,7days of SD respectively, we tested the changes of trends of related indicators of neuroendocrine function, oxidative stress, inflammation in serum and aortic tissue of AS rats in each group. We use the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. At the same time, we observed the physiological, behavioral changes, changes of electrocardiograme and morphological changes of the aorta. We explored that whether the aortic tissue of AS rats will be damaged by SD-induced changes in neuroendocrine function, oxidative stress, response of inflammatory after SD. We explored that whether SD can accelerate the development of plaque rupture leading to acute cardiovascular and cerebrovascular events.
Chapter one:the influence of the changes of neuroendocrine function in atherosclerotic rats after sleep deprivation
Objective:To observed the fluctuations of expression of adrenocorticotropic hormone (ACTH) and cortisol (CORT), two closely related with cardiovascular disease hormones produced by the neuroendocrine system, in the serum at different time under SD, analysis the functional status of HPA axis, and reflect changes of neuroendocrine function in SD rats.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Observed the physiological and behavioral changes in AS rats after SD.
(4) Tested content of ACTH and CORT in serum in AS rats after SD.
Results:
(1) The mental state of AS rats was gradually deteriorated, response dull, loss of appetite, body weight loss gradually, variable weak, fur become rough, unkempt and not gloss, after SD. With the time of SD, AS rats was first excited, then irritated, at the last failure.
(2) The levels of ACTH and CORT in AS rats were in the volatility of changes after SD. Witch is increased at first and then declined.
Conclusions:Stress stimulation caused by SD can activate the HPA axis, stimulated the secretion of ACTH and CORT related closely with cardiovascular risk factors. With the time of SD, levels of hormones secreted were in the volatility of changes, then they feedback to the changes of stress. Thus SD can impact on the cardiovascular system, accelerate the progress of AS in AS rats.
Chapter two:the influence to the levels of oxidative stress in atherosclerosis rats after Sleep deprivation
Objective:Represented by glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase(SOD), four important indicator of oxidative stress, observed oxidative stress and changes in trends in aortic tissue of AS rats under SD. Understand the influence to SD-induced oxidative stress on the process of AS disease in AS rats.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Detected contents of GSH and MDA in aortic tissue of AS rats after SD.
(4) Detected activity of GSH-Px and SOD in aortic tissue of AS rats after SD.
(5) Analyzed the correlation between various indicators and the time of sleep deprivation.
Results:
(1) The content of GSH in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.
(2) The activity of GSH-Px in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.
(3) The activity of SOD in aortic tissue of AS rats was increased significantly and reached the highest value at the first day of SD. With the time of SD, it showed decreasing trend.
(4) The content of MDA in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was negatively correlated with GSH、GSH-Px and SOD (r=-0.949,-0.977,-0.590, P<0.001), and was positively correlated with MDA(r=0.984, P<0.001).
Conclusions:The oxidative stress occurred in AS rats after SD. With the time of SD, the body's antioxidant capacity is gradually weakened, suffered more severe oxidative damage, thus speeding up the development process of AS lesions.
Chapter three:the influence to the levels of inflammatory cytokines in atherosclerosis rats after Sleep deprivation
Objective:We used serum and aortic tissue in AS rats as samples to detect the levels of tumor necrosis factor-a (TNF-a), hypersensitivity-creactive protein (hs-CRP), interleukin-6(IL-6) in serum and expression levels of protein of nuclear factor-kappa B (NF-κB) in aortic tissue, with different times of SD. Understand whether SD can cause inflammation reaction in AS rats with time of SD, and the trend of reaction extent. We explored that whether inflammatory reaction can be activated by SD, so that the process of development will be accelerated by inflammatory reaction.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Detected the levels of TNF-a, hs-CRP, IL-6in serum of AS rats after SD.
(4) Detected the expression levels of protein of NF-κB in aortic tissue of AS rats after SD.
(5) Analyzed the correlation between various indicators and the time of sleep deprivation.
Results:
(1) The levels of TNF-a in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(2) The levels of hs-CRP in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(3) The levels of IL-6in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(4) The expression levels of protein of NF-κB in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was positively correlated with TNF-α、 hs-CRP、IL-6and NF-κB (r=0.952,0.951,0.961,0.986, P<0.001).
Conclusions:Inflammatory reaction was activated in AS rats after SD. Inflammatory reaction sustainable development, and AS lesions in aortic tissue of AS rats deepened with the time of SD. SD can activate inflammatory reaction leading to accelerate the process of development of AS.
Chapter four:the influence to the stability of plaque in atherosclerosis rats after Sleep deprivation
Objective:In this study, we use As rats after SD as the research object, observed the electrocardiogram performance, morphological changes of the aorta by microscope, detected the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. Understand the changes of indicators mentioned above with the time of SD. We explored that whether SD can accelerate the development of plaque rupture leading to accelerate the process of development of AS. Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9. To make sure whether SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, promote the development of plaque rupture leading to accelerate the process of development of AS.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Observed the electrocardiogram performance.
(4) Prepared aorta sample of AS rats and observed it by microscopy after SD.
(5) Detected the expression levels of protein of MMP-9in aortic tissue of AS rats after SD.
(6) Analyzed the correlation between various indicators and the time of sleep deprivation.
(7) Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9.
Results:
(1) The changes of heart rates of AS rats were large after SD. The changes of heart rates of AS rats in volatility of fast at first then slow down with the time of SD.
(2) With the time of SD, ST-T of electrocardiogram elevated gradually, T wave tall and upright showed SD can induce full thickness myocardial ischemia.
(3) With the SD time, the severity of AS in aortic tissue of AS rats increased gradually after SD.
(4) The expression levels of protein of MMP-9in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was positively correlated with the changes of ST-T of electrocardiogram and MMP-9(r=0.883,0.978, P<0.001).
(6) The main factors that can affect the expression levels of protein of MMP-9in aortic tissue of AS rats were ACTH、MDA、hs-CRP and IL-6.
Conclusions:SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, change the expression levels of protein of MMP-9in aortic tissue of AS rats, promote the development of plaque rupture leading to accelerate the process of development of AS.
SD影响了机体固有的生物节律,使机体处于应激状态。应激是机体对各种有害刺激的反应。应激早期机体出现保护防御性的快速动员并处于最佳状态,但持续时间短,随后机体进入抵抗或适应阶段,持续强烈的有害刺激将耗竭机体的抵抗能力,机体内环境明显失衡,应激反应的负效应陆续显现,出现应激相关的疾病、器官功能衰退甚至体克、死亡。
机体受到强烈刺激时,应激反应的神经内分泌改变为蓝斑-去甲肾上腺素能神经元／交感-肾上腺髓质轴和下丘脑-垂体-肾上腺皮质轴(hypothalamus-pituitary-adrenal, HPA)的强烈兴奋。参与应激反应最重要的是HPA轴。HPA轴激活,促进促肾上腺皮质激素释放激素释放,进而刺激促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)的分泌,增加皮质醇(cortisol, CORT)的分泌,HPA轴的活动受到体内外各种应激性刺激的影响而发生改变。ACTH水平直接反映HPA轴的功能状态。CORT是HPA轴的终末产物,对机体的糖、脂肪和蛋白质的代谢有重要影响,因此常作为研究应激的最经典、最重要的指标之一。CORT能直接影响糖、蛋白质、脂肪等三大营养物质代谢,还有抑制免疫作用,增加了心血管系统对儿茶酚胺和其它加压物质的反应性,加强去甲肾上腺素对动脉的收缩作用,促进肝脏生成血管紧张素原,使肾素与之结合而转化为血管紧张素。引起Na+、H2O潴留,增加血容量,引起血压升高。引起白细胞增多,增加氧自由基的产生。而氧自由基损害血管内皮细胞的结构和功能,内皮细胞通透性增加,脂质易于侵入血管内膜,促进AS的发生和发展。近期也有研究提示冠心病的发生发展过程与HPA轴有着密切的关系。
氧化应激是指机体内抗氧化物和氧化物生成系统之间的不平衡。生物体进行有氧代谢时可产生活性氧。正常情况下,体内氧自由基的产生和清除是平衡的,当自由基产生过多或体内抗氧化物相对不足时,体内氧自由基代谢就会出现失衡,自由基在体内累积过多,就会攻击机体,即发生氧化应激。SD可通过多种途径诱发机体的氧化应激。具体包括SD后导致能量消耗代谢及自由基的增多,机体抗氧化能力降低以及通过内质网应激间接引起氧化应激三条途径。氧化应激条件下,儿茶酚胺和糖皮质激素升高,以动员机体各方面的机制来对付应激作用下机体出现自由基产生和清除失衡。自由基在体内大量“堆积”,引发广泛的损伤效应。
动脉粥样硬化(atherosclerosis, AS)是严重危害公众健康的常见病和多发病,近年在我国呈增长趋势。AS是一种发生在大中动脉的疾病,如冠状动脉、颈动脉、四肢末端的动脉和弹性动脉(如主动脉、髂动脉)。粥样斑块可堵塞动脉管腔,且极易发生血栓、出血、栓塞和动脉破裂等,导致严重的后果。目前认为,AS的发生及发展与炎症反应有关。最近研究指出：AS实质上是一种复杂、缓慢进展的炎症过程。炎性反应在AS的发生、发展及最后斑块表面破裂并发血栓形成的所有阶段均具有重要作用。目前有较多关于SD影响炎症因子释放的报道表明SD可促发应激反应而导致各类炎性蛋白释放。而这些炎性蛋白又可危及心血管系统。
近年来,越来越多的证据显示对于急性心脑缺血性临床事件的发生,不稳定AS斑块是较动脉狭窄更危险的因素。急性冠脉综合征的发生常与一些不稳定斑块及继发血栓密切相关,这些斑块常常并不导致严重的管腔狭窄,却容易发生破裂、糜烂、钙化等情况而易于继发血栓导致临床高危事件的发生。在AS损伤中,富含脂质的巨噬泡沫细胞聚集是易破斑块的重要特征,巨噬细胞分泌基质金属蛋白酶(matrix metalloproteinases, MMPs)在斑块破裂中起重要作用。MMPs几乎能降解细胞外基质的所有成分,削弱纤维帽对斑块的保护作用从而促进斑块的破裂。MMPs目前被认为是动脉粥样硬化和冠心病的独立危险因素。MMP-9是MMPs家族中的重要成员,在AS斑块处的血管重构、斑块的不稳定及其破裂诱发的急性冠脉综合征都扮演着重要的角色。
本研究对AS大鼠采用“改良多平台睡眠剥夺法”建立SD模型,分别对其进行1、3、5、7天SD。SD后检测各组AS大鼠血清中及主动脉组织内神经内分泌功能改变、氧化应激、炎症反应的相关指标变化趋势,并以主动脉组织内MMP-9蛋白表达水平作为评价斑块稳定性的指标,同时结合观察SD后各组大鼠的生理、行为改变,心电图变化,主动脉组织形态学改变,以探讨SD后的AS大鼠主动脉组织本身是否因为SD所致的神经内分泌功能改变、氧化应激、炎症反应等而受到损伤,促进斑块的发展、破裂从而导致急性心脑血管事件的发生。
第一章睡眠剥夺对动脉粥样硬化大鼠神经内分泌功能变化的影响
目的：
以神经内分泌系统所产生的两种与心血管疾病密切相关的激素,ACTH及CORT为切入点,通过测定其在血清中的表达量在不同SD时间情况下的波动情况,分析HPA轴功能状态,来反映SD对大鼠神经内分泌功能变化的影响。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、观察SD后AS大鼠的生理及行为改变。
(四)、检测SD后AS大鼠血清ACTH及CORT含量。
结果：
(一)、SD后AS大鼠精神状态逐渐转差,反应变迟钝,食欲不振,身体渐消瘦、变虚弱,皮毛变粗糙、蓬乱而没有光泽。且随着SD时间的延长,AS大鼠呈先兴奋,然后激惹,最后衰竭的变化趋势。
(二)、SD后AS大鼠ACTH及CORT水平呈先增高后下降的波动性变化。
结论：
SD造成的应激性刺激,能够激活HPA轴,并刺激与心血管危险因素密切相关的ACTH及CORT分泌,且随着SD时间的变化,激素分泌水平发生波动,并反馈性地引起应激水平的变化。从而对心血管系统产生影响,促进AS大鼠的AS进展。
第二章睡眠剥夺对动脉粥样硬化大鼠氧化应激水平的影响
目的：
以还原型谷胱甘肽(glutathione, GSH)、脂质过氧化物丙二醛(malondialdehyde, MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)及超氧化物歧化酶(superoxide dismutase, SOD),四种氧化应激的重要指标为代表,观察SD情况下,AS大鼠主动脉组织的氧化应激水平及其变化趋势,了解SD所致的氧化应激对AS大鼠AS病变进程的影响。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、检测SD后AS大鼠主动脉组织GSH及MDA含量。
(四)、检测SD后AS大鼠主动脉组织GSH-Px及SOD活性。
(五)、作各指标与SD时间间的相关性分析。
结果：
(一)、SD后AS大鼠主动脉组织GSH含量降低,且随着SD时间的延长,其含量呈现逐渐降低的趋势。
(二)、SD后AS大鼠主动脉组织GSH-Px活性降低,且随着SD时间的延长其活性呈现逐渐降低的趋势。
(三)、在SDld AS大鼠主动脉组织SOD活性水平明显升高并达到最高值,而后随着SD时间的延长,SOD活性水平降低,呈持续下降趋势。
(四)、SD后AS大鼠主动脉组织MDA含量升高,且随着SD时间的延长,其含量呈现逐渐升高趋势。
(五)、GSH、GSH-Px、SOD与SD时间呈负相关关系(r=-0.949,-0.977,-0.590,P<0.001)。MDA与SD时间呈正相关关系(r=0.984,P<0.001)。
结论：
SD后,AS大鼠发生氧化应激反应,且随着SD时间的延长,机体的抗氧化能力逐渐减弱,所受氧化损伤逐渐加重,从而加速AS病变进程的发展。
第三章睡眠剥夺对动脉粥样硬化大鼠致炎因子水平的影响
目的：
以经过不同时长SD后的AS大鼠血清及主动脉组织为样本,检测随SD时间变化,AS大鼠血清中TNF-α、hs-CRP、IL-6水平及主动脉组织中NF-κB蛋白表达水平的变化情况,以期了解SD是否可以引起AS大鼠机体发生炎症反应,及其反应程度随SD时间的变化趋势,以探讨SD是否可以通过激活炎症反应而促进AS进程的发展。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、检测SD后AS大鼠血清TNF-α、hs-CRP、IL-6水平。
(四)、检测SD后AS大鼠主动脉组织NF-κB蛋白表达水平。
(五)、作各指标与SD时间间的相关性分析。
结果：
(一)、SD后AS大鼠血清中的TNF-α水平升高,且随着SD时间的延长,其水平呈现逐渐升高的趋势。
(二)、SD后AS大鼠血清中的hs-CRP水平上升,且随着SD时间的延长,其水平呈现持续上升的趋势。
(三)、SD后AS大鼠血清中的IL-6水平升高,且随着SD时间的延长,其水平逐渐升高。
(四)、SD后AS大鼠主动脉组织NF-κB蛋白表达水平随着SD时间的延长呈逐渐升高的趋势。
(五)、TNF-α、hs-CRP、IL-6、NF-κB与SD时间均呈正相关关系(r=0.952,0.951,0.961,0.986,P<0.001)。
结论：
SD后,AS大鼠炎症反应激活,且随着SD时间的延长,机体的炎症反应持续发展,主动脉组织AS病变加重。SD可通过激活炎症反应而促进AS病变进程的发展。
第四章睡眠剥夺对动脉粥样硬化大鼠斑块稳定性的影响
目的：
以SD后的AS模型大鼠为研究对象,观察其心电图表现,利用光镜观察其主动脉形态学改变,通过检测其主动脉组织内MMP-9蛋白表达水平作为评价斑块稳定性的指标,以了解随着不同SD时间,上述各项的变化,探讨SD是否促进AS斑块的不稳定,从而促进了AS病变的进程。并用多元逐步回归方法分析前述有关神经内分泌、氧化应激、炎症相关指标中对MMP-9蛋白表达水平有影响的指标,以明确SD是否从神经内分泌、氧化应激、炎症三方面对AS大鼠产生影响,从而促进其AS斑块的不稳定、破裂,加重AS病变的发展。
材料及方法：
(一)、建立AS大鼠模型。
(二)、建立AS大鼠SD模型。
(三)、SD后AS大鼠心电图监测。
(四)、SD后AS大鼠主动脉组织光镜标本制备及观察。
(五)、SD后大鼠主动脉组织MMP-9蛋白表达水平检测。
(六)、作各指标与SD时间间的相关性分析。
(七)、用多元逐步回归方法分析前述有关神经内分泌、氧化应激、炎症相关指标中对MMP-9蛋白表达水平有影响的指标。
结果：
(一)、SD后AS大鼠心率变化较大。随着SD的时间延长,AS大鼠心率呈先增快后减慢的波动性变化。
(二)、随着SD的时间延长,AS大鼠心电图ST-T逐渐上抬,T波高耸直立,显示SD引起心肌全层缺血。
(三)、SD后AS大鼠主动脉AS病变程度随着SD时间的延长而逐渐加重。
(四)、SD后AS大鼠主动脉组织MMP-9蛋白表达水平升高,且随着SD时间的延长,其表达水平呈持续升高的趋势。
(五)、心电图ST-T改变、MMP-9与SD时间呈正相关关系(r=0.883,0.978,P<0.001)。
(六)、通过多元逐步回归分析发现影响AS大鼠主动脉组织MMP-9蛋白表达水平的主要因素为：ACTH、MDA、hs-CRP及IL-6。
结论：
SD可使AS大鼠分别在神经内分泌、氧化应激以及炎症三个方面发生变化,从而导致AS大鼠主动脉组织MMP-9蛋白水平发生改变,从而促进其AS斑块的不稳定、破裂,加重AS病变的发展。
The concept of sleep deprivation (SD) originated in the continuing/continuous working state lead to lack of sleep. It describes a process and status that person loss of the required amount of sleep because of the environment or himsely reasons. Generally, sleep less than6-8hours within24hours, means it take place SD. With the accelerated pace of modern life and social competition, SD become a very important social issue. SD in some occupations or groups is inevitable. We often heard of some reports of heart attack or sudden death at worse due to continuing working and insufficient sleep.
SD can influence the body inherent biological rhythm, so that the body was in stress state. Stress is the body reaction for various kinds of harmful stimulation. The body will occur rapid mobilization of defensive protection and at its best state in early period of stress. However, t he duration is short. Then the body state is going into the resistance or adaptation stage. Noxious stimulation is continuing strongly deplete to the body's resistance. At that time, the internal environment is significantly imbalanced. The negative effects of stress including stress-related diseases, organ function decline, even shock and death have become more obviously.
When body was strongly stimulated, the changes of the neuroendocrine response to stress were the strongly excited of locus coeruleus-norepinephrine neurons/sympathetic-adrenal axis and hypothalamus-pituitary-adrenal (HP A) axis. The role of HPA axis involved in stress response is the most important. When HPA axis was activated, it can accelerate the release of corticotropin releasing hormone, thereby, stimulating the secretion of adrenocorticotropic hormone (ACTH), increased cortisol (CORT) secretion,. Activity of HPA axis can be changed affected by various stress stimuli in vivo and vitro. The levels of ACTH directly reflect the state of HPA axis function. CORT is the end products of HPA axis. It has important implication for glucose, fat and protein metabolism of body. Therefore, it is considered as one of the most classic and important indicators in stress research. CORT can directly affect glucose, protein and fat metabolism, suppress immune function, increased the reactivity of cardiovascular system on catecholamine and other pressurized reactive substances. It also can strengthen of norepinephrine on contraction of the artery, accelerate the liver produce angiotensinogen. It can combine with renin into renin-angiotensin. It caused Na+, H2O retention, increased blood volume, elevated blood pressure. It can induce leukocytosis, increase the production of oxygen free radicals. The oxygen free radical can damage to structure and function of vascular endothelial cells. When the permeability of endothelial cells Increased, it lead lipid can easily invade intima, then the occurrence and development of AS is accelerated. Recent researches have reported that occur and development process of coronary heart disease is closely related to HPA axis.
Oxidative stress means imbalance between body antioxidants and the oxide generating system. Organisms can produce reactive oxygen species when they are doing for aerobic metabolism. Under normal circumstances, the production and clear of oxygen free radicals in vivo is balanced. When too many free radicals or antioxidants in vivo relatively low, free radicals in the body will imbalance. When the accumulation of free radicals in the body is excessively, it will attack the body, that is, oxidative stress. SD can induce oxidative stress by a variety of ways. Three ways, specifically including the cause of energy metabolism and expenditure and the increase in free radicals after SD, reduced antioxidant capacity as well as through the endoplasmic reticulum stress induced oxidative stress indirectly. In oxidative stress conditions, elevated catecholamine and glucocorticoid can mobilize the body in all aspects of the mechanism to cope with the free radical generation and scavenging imbalance occur in the body. A large number of free radicals accumulation in the body, then they caused extensive damage.
Atherosclerosis (AS) is a common and frequently-occurring disease, it is seriously harm to public health. In recent years, AS has an increasing trend in China. AS is a disease in large and medium arteries, such as coronary, carotid arteries, the arteries of the extremities and elastic arteries (e.g. aorta, iliac arteries), arterial lumen can be blocked by Atherosclerotic plaques. As is a disease prone to blood clots, bleeding, thrombosis and arterial rupture, it can lead to serious consequences. Currently considered that the occurrence and development of AS is related to inflammatory reaction. Recent studies have pointed out that AS is essentially a complex, slow progress of the inflammatory process. Inflammation is playing an important role in all stages of AS, including the occurrence and development of AS, plaque surface rupture and finally complicated with thrombosis. There are more reports about SD affects the release of inflammatory cytokines, indicate that SD can trigger the stress response which led to the release of various inflammatory protein. These inflammatory proteins can also endanger the cardiovascular system.
In recent years, more and more evidence of acute cerebral and cardiac ischemia clinical events, indicated that AS unstable plaques is a more dangerous factor than arterial stenosis. The occurrence of acute coronary syndrome is often closely related to some unstable plaques and secondary thrombosis. These patches often do not lead to severe stenosis, it prone to rupture, erosion, calcification, etc. and easily to secondary thrombosis, lead to the clinical high risk events. Accumulation of lipid-rich macrophage foam cells in AS Injury is an important feature of plaque easy to break. Macrophages secrete matrix metalloproteinase (MMPs), witch play an important role in plaque rupture. MMPs are now thought as an independent risk factor of atherosclerosis and coronary heart disease, MMP-9is an important member of the family of MMPs. MMP-9plays an important role in vascular remodeling in AS plaque, unstable plaque and its rupture induced acute coronary syndrome.
In this study, we used "modified multiple platform method of SD" to establish SD model with AS rats. After1,3,5,7days of SD respectively, we tested the changes of trends of related indicators of neuroendocrine function, oxidative stress, inflammation in serum and aortic tissue of AS rats in each group. We use the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. At the same time, we observed the physiological, behavioral changes, changes of electrocardiograme and morphological changes of the aorta. We explored that whether the aortic tissue of AS rats will be damaged by SD-induced changes in neuroendocrine function, oxidative stress, response of inflammatory after SD. We explored that whether SD can accelerate the development of plaque rupture leading to acute cardiovascular and cerebrovascular events.
Chapter one:the influence of the changes of neuroendocrine function in atherosclerotic rats after sleep deprivation
Objective:To observed the fluctuations of expression of adrenocorticotropic hormone (ACTH) and cortisol (CORT), two closely related with cardiovascular disease hormones produced by the neuroendocrine system, in the serum at different time under SD, analysis the functional status of HPA axis, and reflect changes of neuroendocrine function in SD rats.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Observed the physiological and behavioral changes in AS rats after SD.
(4) Tested content of ACTH and CORT in serum in AS rats after SD.
Results:
(1) The mental state of AS rats was gradually deteriorated, response dull, loss of appetite, body weight loss gradually, variable weak, fur become rough, unkempt and not gloss, after SD. With the time of SD, AS rats was first excited, then irritated, at the last failure.
(2) The levels of ACTH and CORT in AS rats were in the volatility of changes after SD. Witch is increased at first and then declined.
Conclusions:Stress stimulation caused by SD can activate the HPA axis, stimulated the secretion of ACTH and CORT related closely with cardiovascular risk factors. With the time of SD, levels of hormones secreted were in the volatility of changes, then they feedback to the changes of stress. Thus SD can impact on the cardiovascular system, accelerate the progress of AS in AS rats.
Chapter two:the influence to the levels of oxidative stress in atherosclerosis rats after Sleep deprivation
Objective:Represented by glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase(SOD), four important indicator of oxidative stress, observed oxidative stress and changes in trends in aortic tissue of AS rats under SD. Understand the influence to SD-induced oxidative stress on the process of AS disease in AS rats.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Detected contents of GSH and MDA in aortic tissue of AS rats after SD.
(4) Detected activity of GSH-Px and SOD in aortic tissue of AS rats after SD.
(5) Analyzed the correlation between various indicators and the time of sleep deprivation.
Results:
(1) The content of GSH in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.
(2) The activity of GSH-Px in aortic tissue of AS rats was reduced after SD. With the time of SD, it showed decreasing trend.
(3) The activity of SOD in aortic tissue of AS rats was increased significantly and reached the highest value at the first day of SD. With the time of SD, it showed decreasing trend.
(4) The content of MDA in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was negatively correlated with GSH、GSH-Px and SOD (r=-0.949,-0.977,-0.590, P<0.001), and was positively correlated with MDA(r=0.984, P<0.001).
Conclusions:The oxidative stress occurred in AS rats after SD. With the time of SD, the body's antioxidant capacity is gradually weakened, suffered more severe oxidative damage, thus speeding up the development process of AS lesions.
Chapter three:the influence to the levels of inflammatory cytokines in atherosclerosis rats after Sleep deprivation
Objective:We used serum and aortic tissue in AS rats as samples to detect the levels of tumor necrosis factor-a (TNF-a), hypersensitivity-creactive protein (hs-CRP), interleukin-6(IL-6) in serum and expression levels of protein of nuclear factor-kappa B (NF-κB) in aortic tissue, with different times of SD. Understand whether SD can cause inflammation reaction in AS rats with time of SD, and the trend of reaction extent. We explored that whether inflammatory reaction can be activated by SD, so that the process of development will be accelerated by inflammatory reaction.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Detected the levels of TNF-a, hs-CRP, IL-6in serum of AS rats after SD.
(4) Detected the expression levels of protein of NF-κB in aortic tissue of AS rats after SD.
(5) Analyzed the correlation between various indicators and the time of sleep deprivation.
Results:
(1) The levels of TNF-a in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(2) The levels of hs-CRP in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(3) The levels of IL-6in serum of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(4) The expression levels of protein of NF-κB in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was positively correlated with TNF-α、 hs-CRP、IL-6and NF-κB (r=0.952,0.951,0.961,0.986, P<0.001).
Conclusions:Inflammatory reaction was activated in AS rats after SD. Inflammatory reaction sustainable development, and AS lesions in aortic tissue of AS rats deepened with the time of SD. SD can activate inflammatory reaction leading to accelerate the process of development of AS.
Chapter four:the influence to the stability of plaque in atherosclerosis rats after Sleep deprivation
Objective:In this study, we use As rats after SD as the research object, observed the electrocardiogram performance, morphological changes of the aorta by microscope, detected the expression levels of protein of MMP-9in aortic tissue as an indicator for evaluating plaque stability. Understand the changes of indicators mentioned above with the time of SD. We explored that whether SD can accelerate the development of plaque rupture leading to accelerate the process of development of AS. Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9. To make sure whether SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, promote the development of plaque rupture leading to accelerate the process of development of AS.
Methods:
(1) Established rat model of AS.
(2) Established AS rat model of SD.
(3) Observed the electrocardiogram performance.
(4) Prepared aorta sample of AS rats and observed it by microscopy after SD.
(5) Detected the expression levels of protein of MMP-9in aortic tissue of AS rats after SD.
(6) Analyzed the correlation between various indicators and the time of sleep deprivation.
(7) Analyzed related indicators of neuroendocrine function, oxidative stress and inflammation mentioned above by multiple stepwise regression method to find out indicators that can influence the expression levels of protein of MMP-9.
Results:
(1) The changes of heart rates of AS rats were large after SD. The changes of heart rates of AS rats in volatility of fast at first then slow down with the time of SD.
(2) With the time of SD, ST-T of electrocardiogram elevated gradually, T wave tall and upright showed SD can induce full thickness myocardial ischemia.
(3) With the SD time, the severity of AS in aortic tissue of AS rats increased gradually after SD.
(4) The expression levels of protein of MMP-9in aortic tissue of AS rats was increased after SD. With the time of SD, it showed increasing trend.
(5) The time of sleep deprivation was positively correlated with the changes of ST-T of electrocardiogram and MMP-9(r=0.883,0.978, P<0.001).
(6) The main factors that can affect the expression levels of protein of MMP-9in aortic tissue of AS rats were ACTH、MDA、hs-CRP and IL-6.
Conclusions:SD can influence AS rats by tress aspects, neuroendocrine function, oxidative stress and inflammation, change the expression levels of protein of MMP-9in aortic tissue of AS rats, promote the development of plaque rupture leading to accelerate the process of development of AS.
引文
1.张亚晶,卢才义.睡眠剥夺对心血管系统的影响及其研究进展.中华老年多器官疾病杂志,2008,6：529-532.
2. Benington JH, Heller HC. Does the function of REM sleep concern non-REM sleep or waking? Prog Neurobiol.1994,44(5):433-449.
3.赵忠新,主编.临床睡眠障碍学.第一版.上海：第二军医大学出版社,2003：30-710.
4. Simpson N, Dinges DF. Sleep and inflammation. Nutrition Reviews,2007,65(3): 244-252.
5. Hublin C. Parinen M, Koskenvuo M, et al. Sleep and mortality:a population-based 22-year follow-up study. Sleep,2007,30(12):1245-1253.
6. Van Dort CJ. Baghdoyan HA. Lydic R. Adenosine A(1) and A(2A)receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci,2009,29(3):871-881
7. Altena E, Ramautar JR, Van Der Werf YD, et al. Do sleep complaints contribute to age-related cognitive decline? Prog Brain Res.2010,185:181-205.
8.张亚晶,卢才义,黄亚.睡眠剥夺对大鼠心脏的影响及其致心律失常机制研究.血管康复医学杂志,2009,18(3),224-226.
9. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Me d,2003,163:205-209.
10. Holmes AL, Burgess HJ, McCulloch K, et al. Day-time cardiac autonomic activity during one week of continuous night shift. J Hum Ergol(Tokyo),2001,30: 223-228.
11. Lusardi P, Zoppi A, Preti P, el al. Efects of insuficient sleep on blood pressure in hypertensive patients:a 24-h study. Am J Hypertens,1999,12:63-68.
12. Takase B, Akima T, Satomura K, el al. Efects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother,2004,58:S35-S39.
13. Liu Y, Tanaka H, et al. Overtime work, insufficient sleep, and risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med.2002,59(7): 447-451.
14. Irwin MR, Ziegler M. Sleep deprivation potentiates activation of cardiocascular and catecholamine responses in abstinent alcoholics. Hypertention.2005,45(2): 252-257.
15. Holmes AL, Burgess HJ, Dawson D. Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature. Appl Physiol.2002,92(6): 2578-2584.
16.钟旭,肖毅,黄蓉,等.整夜完全睡眠剥夺对心血管自主神经活动的影响.中华内科杂志,2005,44：577-580.
17.柴慧娟,徐淑梅,杨海贤.睡眠剥夺对人鼠心肌超微结构损伤效应的研究.武警医学,2008,19：24-27.
18.柴慧娟,徐淑梅.睡眠剥夺对人鼠心肌损伤效应和抗氧化指标的影响.中国应用生理学杂志,2008,24：71-75.
19. Kato M, Phillips BG, Sigurdsson G, et al. Effects of sleep deprivation on neural circulatory control. Hypertension,2000,35:1173-1175.
20. Lusardi P, Mugellini A, Preti P, et al. Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects. Am J Hypertens, 1996,9:503-505.
21. Chen HI. Efiects of 30-h sleep loss on cardiorespiratory functions at rest an d in exercise. Med Sci Sports Exere,1991,23:193-198.
22 Vgontzas AN, Mastorakos G, Bixler EO, et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes:potential clinical implications. Clin Endocrinol(Oxf),1999.51:205-215.
23. Tochikubo O, Ikeda A, Miyajima E, et al. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension,1996,27: 1318-1324.
24. Ayas NT, White DP, Al-Delaimy WK, et al. A prospective study of self reported sleep duration and incident diabetes in women. Diabetes Care.2003.26:380-384.
25. Palma BD, Gabriel A JR, Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35:75-79.
26.曹雪亮,苗丹民,皇甫恩,等.高原与平原条件下48h完全睡眠剥夺对血压和心率的影响.解放军预防医学杂志,2003,21：334-336.
27. Perry JC, D'Almeida V, Souza FG, et al. Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats. Respir Physiol Neurobiol,2007,156:250-258.
28. Andersen ML, Martins PJ, D'Almeida V, et al. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp Gerontol,2004,39:817-824.
29. VanHelder T, Symons JD, Radomski MW. Effects of sleep deprivation and exercise on glucose tolerance. Aviat Space Environ Med,1993,64(6):487-492.
30. VanHelder T, Radomski MW. Sleep deprivation and the effect on exercise performance. Sports Med,1989,7(4):235-247.
31. Yeh ET, Willerson JT. Coming of age of C-reactive protein:using inflammation markers in cardiology. Circulation.2003,107(3):370-371.
32. Epstein SE, Zhu J, Najafi AH, et al. Insights into the role of infection in atherogenesis and in plaque rupture. Circulation,2009,119(24):3133-3141.
33. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol.2004, 43(4):678-683.
34.段小莉,王百忍,杨唐斌等.抗CRF单克隆抗体和多克隆抗体的制备及其在睡眠剥夺模型大鼠脑内的变化.细胞与分子免疫学杂志,2005,21：476.
35.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第一军医大学学报,2007,28(2)：201-203.
36. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
37. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
38. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol.2002,80(3):193-197.
39. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol.1995, 50(10):1557-1565.
40.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
41. Naidoo N, Giang W, Galante RJ,et al. Sleep deprivation induces the unfolded protein response in muse cerebral cortex. J Neurochem.2005,92 (5):1150-1157.
42. Tononi G, Cirelli C. Modulation of brain gene expression during sleep and wakefulness:a review of recent indings. Neuropsychopharmacology.2001,25: S28-S35.
43. Shaw PJ, Cirelli C, Greenspan RJ et al. Correlates of sleep and waking in Drosophila melanogaster. Science.2000,287:1834-1834.
44. Terao A, Steininger TL, Hyder K, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience.2003,116:187-200.
45. Xu C, Bailly-Maitre B. et al. Endoplasmic reticulum stress:cell life and death decisions J. Clin. Invest.2005,115:2656-2664.
46. Thomas RD, Kaufman RJ. A trip to the ER:coping with stress. Trends Cell Biol. 2004,14:20-28.
47. kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest,2002,110:1389-139.
48. Luke Wi, seman R, Ralch WE. A new pharmacology-drugging stressed folding pathways. TRENDS in Molecular Medicine,2005,8:347-350.
49. Jung HY, Wek RC. Phosphorylation of the a-subunit of the eukaryotic initiation factor-2 reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. The Journal of biological chemistry,2005,14:14189-14202.
50. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling:the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol,2006,38:317.
51. Glass ck, Witztum JL. Atherosclerosis, the road ahead. Cell,2001,104:503.
52. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
53. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
54. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
55. Nikkari ST, O'Brien KD, Ferguson M, et al. Interstitial collagenase (MMP-1) in human carotid atherosclerosis. Circulation,1995,92:1393-1398.
56. Empana JP, Jouven X, Canoui-Poitrine F, et al. C-Reactive protein, interleukin 6, fibrinogen and risk of sudden death in european middle-aged men:the PRIME study. Arterioscler Thromb Vasc Biol,2010,30(10):2047-2052.
57. Wassel CL, Barrett-Connor E, Laughlin GA. Association of circulating C-reactive protein and interleukin-6 with longevity into the 80s and 90s:the rancho bernado study. J Clin Endocrinol Metab,2010,95(10):4748-4755.
58. Hamer M, Chida Y, Stamatakis E. Association of very highly elevated C-reactive protein concentration with cardiovascular events and all-cause mortality. Clin Chem, 2010,56(1):132-135.
59. Elkind MSV. Inflammatory mechanisms of stroke. Stroke suppl,2010,41(10): S3-S8.
60. Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality:an individual participant meta-analysis. Lancet.2010,375(9709):132-140.
61. Lagrand WK. Niessen HW. Wblbink GJ, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation, 1997,95:97-103.
62.温先勇,杭永伦,薜莉等.冠心病患者C-反应蛋白、一氧化氮、白细胞介素-6测定的临床意义.中国现代医学杂志,2003,13(1)：69-70.
63. Tezono K, Sarker KP, Kikuchi H, et al. Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001;31(2):71-79.
64. Mullenix PS, Andersen CA, Stames BW. Atherosclerosis as inflammation. Ann Vase Surg,2005,19(1):130-138.
65. Shin MH, Moon YJ, Seo JE, et al. Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression. Free Radic BiolMed,2008,44(4): 635-645.
66. Azumi H, Inoue N, Ohashi Y, et al. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris:Important role of NAD(P)H oxidase. Arterioscler Thromb Vase Biol,2002,22:1838-1844.
67. Channon KM. Oxidative stress and coronary plaque stability. Arterioscler Thromb Vase Biol,2002,22:1751-1752.
68. Steinberg D. Low density lipoprotein oxidation its pathobiological significance. J Biol Chem,1997,272(34):20963-20966.
69. Cominacini L, Ulisse G, Pasini AF, et al. Antioxidants inhibit the expression of intercellular cell adhension molecula-1 and vascular cell adhension molecule-1 induced by oxidized LDL on human umbilical endothelial cells. Free Radic Biol Med, 1997,22(1-2):117-127.
70. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res,1999,85(8):753-766.
71. Lawrence de Koning AB, Werstuck GH, Zhou J, et al. Hyper homocysteinemia and its role in the evelopment of artherosclerosis. Clin Biochen,2003,36(6):431.
72. Galis ZS, Muszynski M, Sukhova GK, et al. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci.1995,748:501-507.
73. Rajagopalan S, Meng XP, Ramasamy S, et al. Reactive oxygen species p reduced bymacrophage-derived foam cells regulate the activity of vascularmatrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest,1996,98:2572-2579.
74. Braunwald E. Shattuck Lecture-cardiovascular medicine at the turn of the millennium:triumphs concerns and opportunities. N Engl J Med,1997,337: 1360-1369.
1. Youngblood BD, Zhou J, Smagin GN, et al. Sleep deprivation by the "flower pot" technique and spatial reference memory. Physiol Behav.1997,61(2):249-56.
2.王园园,龙民慧,邹民吉,等.大鼠动脉粥样硬化动物模型的建立和评价.中国实验动物学报,2008,16(6)：421-423.
3.杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立.第二军医大学学报,2003,24(7)：802-804.
4.刘磊,焦向英,张炜芳,等.高脂饲料及维生素D3联合应用建立大鼠动脉粥样硬化模型.山西医科大学学报,2005,36(6)：681-683.
5. Palma BD, Gabriel AJr, Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35(1):75-79.
6. Dou W, Zhao ZX, Miao MY, et al. The effect of sleep deprivation on cognitive and cerebral mitochondrial repiratory function in rats. Neuroscience Bulletin,2005,21(3): 204-209.
7. Suchecki D, Tufik S. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Bchav,2000,68 (3):309-316.
8.黄建欧,赵忠新.大鼠睡眠剥夺方法的研究进展.中华神经医学杂志,2004,3(3)：229-231.
9. Bennani-Kabchi N, Kehel L, EI Bouayadi F, et al. New model of atherosclerosis in insulin resistant sand rats:hypercholesterolemia combined with D2 vitamin. Atherosclerosis,2000,150(1):55-61.
10.沈丽,卢维晨,姚俊宇,等.不同方法建立动脉粥样硬化大鼠模型的比较.心脏杂志,2005,17(1)：18-20.
11.温进坤,韩梅,杜玮南.一种快速建立大鼠动脉粥样硬化模型的实验方法.中国老年学杂志,2001,21,50-52.
12.杨鹏远,丙耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立.第二军医大学学报,2003,24(7)：802-804.
13.郭延松,吴宗贵,杨军柯,等.三种大鼠动脉粥样硬化模型复制方法的比较.中国动脉粥样硬化杂志,2003,11(5)：465-469.
14. Schwierin B, Borbeley AA, Tobler I, et al. Effects of N6-cyclopentyladenosine and caffeine on sleep regulation in the rat. Eur J Pharmacol,1996,300:163-171.
15. Gonzalez MM, Valatx J L, Debilly G Role of the locus coeruleus in the sleep rebound following two different sleep deprivation methods in the rat. Brain-Res,1996, 740(1-2):215-226.
16. Charifi C, Paut-Pagano L, Debilly G, et al. Effect of noradrenergic denervation of the amygdala upon recovery after sleep deprivation in the rat. Neurosci-Let,2000, 287(1):41-44.
17. Deborah Suchecki, Sergio Tufik. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiology& Behavior,2000,68:309-316.
18.吴兴曲,杨来启.睡眠剥夺对大鼠学习能力的影响及机制初步研究.解放军预防医学杂志,2002,20(4)：241-243.
19.刘长云,王海明,陈坚,等.大鼠睡眠剥夺后行为及丘脑诱生型一氧化氮合酶mRNA表达的变化.第二军医大学学报,2002,23(3)：281-283.
20. Taylor LR, Costanzo DJ. Social dominance, adrenal weight, and the reticuloendothelial system in rats. Behav Biol,1975,13:167-174.
21. Suchecki D, Hipo lide DC, Lobo LL, et al. ACTH and corticosterone responses to multiple and single platform techniques-induced REM sleep deprivation. Sleep Research,1995,24:455.
22. Nunes Jr G, Tufik S. Validation of modified multiple platform methods (MPM) of paradoxical sleep deprivation in rats. Sleep Research,1994,23:419.
23.刘永学,高月.应激研究进展.中国病理生理杂志,2002,18：218-221.
24. Taheri S, Lin L, Austin D, et al. Short sleep duration is associated with reduced leptin, elecated ghrelin, and increased body mass index. PLoS Med,2004,1(3): 62-79.
25.孙慧,姚明辉.睡眠不足及夺眠引起机体生理功能的变化.世界临床药物,2009,30(4)：233-236.
26.姚泰主编.生理学5版.北京：人民卫生出版社,2003,398-399.
27.刘卫,钱令嘉,杨志华,等.慢性温和应激抑郁模型大鼠5-羟色胺、色氨酸和应激激素的变化.中国应用生理学杂志,2006,22(2)：169-172.
28.胡淑芳,王惠利,杨来启,等.急性高原应激大鼠脑组织NO, SOD及血浆皮质醇的含量变化.中国心理卫生杂志,2002,16(8)：518-519.
29.周爱军,罗海吉,卢晓翠,等.L-精氨酸对热应激大鼠血清皮质醇变化的影响.中国公共卫生,2005,21(5)：594-595.
30.杨惠芳,张银娥,刘秀芳等.慢性心理应激对大鼠行为及血清皮质醇影响及运动的调节作用.工业卫生与职业病,2008,34(3)：133-136.
31.季乃军,方宗桥,王成尧,等.原发性高血压患者血清皮质醇测定及其临床意义.河北医学,1995,1(5)：295-297.
32.程志平.内分泌生理学.北京：人民卫生出版社,1984：193.
33.吴淑杰,张雪峰,许丽华,等.高血压和冠心病患者的血清皮质醇浓度测定.吉林医学院学报,1996,16(4)：28-29.
34.吴木潮,黄宾协,黎锋,等.代谢综合征患者血清和尿皮质醇水平与心血管危险因素的关系.广东医学.2006,27(2)：206-207.
35.李丛丛.怒志对冠心病心绞痛患者神经-内分泌-免疫机制的研究.山东：山东中医药大学.2008：16.
36.刘雁峰,王天芳,杨维益,等.复合应激因素致大鼠促肾上腺皮质激素和皮质酮含量变化的研究.中国医药学报.2000,15(1)：72-73.
37.王莹,杨祖铭,朱海娟,等.外源性褪黑素对缺氧缺血性脑损伤新生大鼠血浆促肾上腺皮质激素和皮质酮的影响.实用儿科临床杂志,2008,23：430-432.
38. Choi DC, Evanson NK, Furay AR, et al. The anteroventral bed nucleus of the stria terminalis differentially regulates hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Endocrinology,2008,149(2):818-26.
1. Everson CA, Wehr TA. Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat. Am J Physiol.1993,264(2):376-387.
2. Droge W. Free radicals in t he physiological control of cell function. Physiol Rev, 2002,82:47-95.
3. Murrant CL, Reid MB. Detection of reactive oxygen and reactive nitrogen species in skeletal muscle. Microsc Res Tech,2001,55:236-248.
4. Schulz JB, Lindenau J, Seyfried J, et al. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem,2000,267:4904-4911.
5. Ran Q T, Liang HY, Gu MJ, et al. Transgenic mice over expressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem, 2004,279:55137-55146.
6. Bergamini CM, Gambetti S, Dondi A, et al. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des.2004,10(14):1611-1626.
7. Bauer V, Bauer F. Reactive oxygen species as mediators of tissue protection and injury. Gen Physiol Biophys.1999,18:7-14.
8.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第二军医大学学报.2007,28(2)：201-203.
9. Chang HM, Mai FD, Chen BJ, et al. Sleep deprivation predisposes liver to oxidative stress and phospholipid damage:a quantitative molecular imaging study. J Anat,2008,212(3):295-305.
10. Kumar A, Singh A. Possible involvement of GABA ergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice. Fundam Clin Pharmacol,2009,23(4):439-448.
11. Findrik Z, Vrsalovic Presecki A, Vasic Racki D. Mathematical modelling of NADH oxidation catalyzed by new NADH oxidase from Lactobacillus brevis in continuously operated enzyme membrane reactor. J Biosci Bioeng,2007,104 (4): 275-280.
12.朱秉匡,钟毅,郑仕富,等.益寿调脂片调脂和抗自由基损伤的研究.广州中医药大学学报,1999,16(1)：13-16.
13.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
14. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
15. Abilio VC, Vera JA Jr, Ferreira LS, et al. Effects of melatonin on orofacial movements in rats. Psychopharmacology (Berl),2002,161(4):340-347.
16. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
17. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
18. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol,2002,80(3):193-197.
19. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
20. Kalonia H, Bishnoi M, Kumar A. Possible mechanism involved in sleep deprivation-induced memory dysfunction. Methods Find Exp Clin Pharmacol,2008, 30(7):529-535.
21. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol,2005,25 (1):29-38.
22. Papaharalambus CA, Griendling KK. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med,2007,17(2): 48-54.
23. Armando R, Hector F, Lamberto R, et al. Oxidative Stress at the VascularWall. Mechanistic and Pharmacological Aspects. Archives of Medical Research,2006, (37): 436-448.
24. Chappell DC, Varner SE, Nerem RM, et al. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res,1998,82 (5): 532-539.
25. Galis ZS, Asanuma K, Godin D, et al. Nacetylcysteine decreases the matrix-degrading capacity of macrophage - derived foamcells:new target for antioxidant therapy? Circulation,1998,97(24):2445-2453.
1.芮耀诚.抗动脉粥样硬化药物的研究进展.国外医学：药学分册.1995,22：257-261.
2. Ross R. Atherosclerosis-an inflammatory disease. N Engl Med,1999,340 (2): 115-126.
3. Laurila A, Bloigu A, Nayha SI. Association of helicobacter pylori infection with elevated serum lipids. Atherosclerosis,1999,142(11):207-210.
4.汤耀法.光密度的由来及其物理意义.中国医学物理学杂,1997,14(3)：179-181.
5. Tung A, Herrera S, Bergmann BW, eL al. Can recovery from sleep deprivation occur during general anesthesia. Sleep,2003.26(12):1448.
6. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immunemediated inflammation. N Engl J Med,1995,332:1351-1362.
7. McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med, 1998,338:171-179.
8.Turk Rhen, John A, Cidlowski. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med,2005,353:1711-1723.
9. Nels on LE, Lu J, Guo T, et al. The alpha2-adenocepteragonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology,2003,98(4):428.
10. Tanase D, Baghdoyan HA, Lydic R. Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time. Anesthesiology,2003,98(6):912.
11. Meier-Ewert HK. Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol,2004,43: 678-683.
12. Irwin MR, Wang M, Campomayor CO, et al. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med, 2006,166:1756-1762.
13. Prey DJ, Fleshner M, Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun, 2007,21:1050-1057.
14. Munro JM, Cotran RS. The pathogenesis of atherosclerosis:atherogenesis and inflammation. Lab Invest,1988,58(3):249-619.
15. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
16. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
17. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
18.李巧汶.炎症与组织因子在冠心病中的研究进展.心血管病学进展,2008,29(1)：61-63.
19. Mullenix PS, Andersen CA, Starnes BW. Atherosclerosis as inflammation. Ann Vase Surg,2005,19(1):130-138.
20. Koenig W, Khuseyinova N, Baumert J, et al. Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women:results from the MONICA/KORA Augsburg case-cohort study,1984-2002. Arterioscler Thromb Vasc Biol,2006,26(12): 2745-2751.
21. Hamer M, Chida Y, Stamatakis E. Association of very highly elevated C-reactive protein concentration with cardiovascular events and all-cause mortality. Clin Chem, 2010,56(1):132-135.
22. Elkind MSV. Inflammatory Mechanisms of Stroke. Stroke suppl,2010,41(10): S3-S8.
23. Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality:an individual participant meta-analysis. Lancet,2010,375(9709):132-140.
24. Jarvisalo M, Harmoinen A, Hakanen M, et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol, 2002,22:1323-1328.
25. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease:application to clinical and public health practice:Astatement for health care professionals from the Centers for Disease Control and Prevention and the American HeartAssociation. Circulation,2003,107(3):499-511.
26. Cushman M, Arnold AM, Psaty BM, et al. C-reactive protein and the 10-year incidence of coronary heart disease in older men and women. Circulation,2005,112: 25-31.
27. Koenig W, Lowel H, Baumert J, et al. C-reactive protein modulates risk prediction based on the Framingham Score:implications for future risk assessment: results from a large cohort study in southern Germany. Circulation,2004,109(11): 1349-1353.
28.崔健昆,那坤.C反应蛋白与冠心病的相关性的研究.世界中西医结合杂志, 2010,5(1)：70.
29. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease:application to clinical and public health practice:Astatement for health care professionals from the centers for disease control and prevention and the american heart association. Circulation,2003,107(3):499-511.
30. Tezono K, Sarker KP, Kikuchi H, et al. Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001; 31(2):71-79.
31. Funayama H, Ishikawa SE, Kubo N, et al. Increases in interleukin-6 and matrix metalloproteinase-9 in the infarct-related coronary artery of acute myocardial infarction. Circ J,2004,68(5):451-454.
32. Szekanecz Z, Kerekes G, Der H, et al. Accelerated atherosclerosis in rheumatoid arthritis. Ann N YAcad Sci,2007,1108:349-358.
33.王育珊,王骥,王广.急险心肌梗死患者缺血-再灌注过程中血清白细胞介素-6,白细胞介素-8的动态变化及意义.中华心血管病杂志,2004,32：1.
34. Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis:a comprehensive review of studies in mice. Cardiovasc Res,2008,79(3):360-376.
35. Petrovay F, Heltai K, Kis Z, et al. Chronic infections and histamine, CRP and IL-6 levels after percutaneous trans luminal coronary angioplasty. Inflamm Res,2007, 56(9):362-367.
36. Mysliwska J, Wieckiewicz J, Hak L, et al. Interleukin 6 polymorphism corresponds to the number of severely stenosed coronary arteries. Eur Cytokine Netw, 2006,17(3):181-188.
37.洪永敦,黄衍寿,吴辉,等.冠心病中医证候与炎症因子关系的临床研究.广州中医药大学学报,2005,22(2)：81-86.
38. Kanters E, Gijbels MJ, Vergouwe MN, et al. Hematopoietic NF-κB deficiency results in small atherosclerotic lesions with an inflanmlatory phenotype. Blood,2004, 103(3):934-940.
39. Bolick DT, Sfinivasan S, Whetzel A, et al. Lipoxygenase Mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of NF-κB. Arterioscler Thromb Vasc Biol,2006,16(4):16.
40. Rook MF, Neuby AC, Southgate KM. Expression of intercellular adhesion molecules in human saphenous veins:effects of inflammatory cytokines andneointima formation in culture. Atherosclcrosis,2000,150(4):33-41.
41. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell,1986,46(5):705-716.
42. Brand K, Page S, Rogler G, et al. Activated transcription factor-kappa B is present in the atherosclerosis lesion. J Clin Invest,1996,97(7):1715-1722.
43. Rodriguez-Porel M, Leman LO, Holmes DR, et al. Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial function in hypercholesterolemic pigs. Cardiovasc Res,2002,53: 1010-1018.
44. Sun Juan, Huang YQ. Role of nuclear kappa B signal pathways in process of atherosclerosis. Modem Journal of Integrated Traditional Chinese and Western Medicine,2007,16(15):2158-2162.
45. Ping D, Boekhoudt GH, Rogers EM, et al. Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte Chemoattractant-1 gene. Immunol,1999,162(2):727-734.
46. Menno PJ, De Winther, Edwin Kanters, Georg Kral, et al. Nuclear factor-KB Signaling in Atherogenesis. Arterioscler Thromb Vasc Biol,2005,25:904-914.
47. Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of ciselement "de-coy" against nuclear factor-KB binding site prevents myocardial infaction. Nat Med,1997,3(8):894-899.
48. Calabro P, Cirillo P, Limongelli G,et al. Tissue factor is induced by resistin in human coronary artery endothelial cells by the NF-KB-dependent pathway. J Vasc Res, 2011,48(1):59-66.
49. Real JT, Martinez-Hervas S, Garcia-Garcia AB, et al. Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia. Eur J Clin Invest,2010,40(2):89-94.
50. Sanchez-Galan E, G6mez-Hernandez A, Vidal C, et al. Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis. Cardiovasc Res.2009,81(1):216-225
1. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient. A call for new definition and risk assessment strategies:part I and part Ⅱ. Circulation, 2003,108:1664-1778.
2.胡大一.急性冠状动脉综合征的治疗新对策和新模式.中国介入心脏病学杂志,2002,10(1)：3.
3. Loftμs IM, Naylor AR, Goodall S. Increased matrixmetalloproteinases-9 activity in unstable carotid plaque. A potential role on acute plaque disruption. Stroke,2003,31 (1):40-47.
4. Funayama H, Ishikawa SE, Kubo N, et al. Increases in interleukin-6 and matrix metallop roteinases-9 in the infarct-related coronary artery of acute myocardial infarction. Circ J,2004,68(5):451-454.
5. ManginasA, Bei E, Chaidaroglou A, et al. Peripheral level of matrixmetalloproteinases-9, interleukin-6 and C-reactive protein are elevated in patients with acute coronary syndromes:correlations with serum troponin I. Clin Cardiol,2005,28(4):182-186.
6. Berul CI, Aronovitz MJ, Wang PJ, et al. In vivo cardiac electrophysiology studies in the mouse. Circulation,1996,94(10):2641-2648.
7.施新酞,等.医学动物实验方法.北京：人民卫生出版社,1979：304.
8.徐叔云,卞如濂,陈修等.药理实验方法学,第三版.北京：人民卫生出版社,2002：1007-1013.
9. Stamler JS, Goldman ME, Gomes J,et al. The effect of stress and fatigue on cardiac rhythm in medical interns. J Electrocardiol.1992,25(4):333-338.
10. Bolli R, Oxygen-derived free radicals and myocardial reperfusion injury:an overview. Cardiovasc Drugs Ther,1991,5(Suppl 2):249-268.
11. Kerr ME, Bender CM, Monti EJ. An introduction to oxygen free radicals. Heart Lung,1996,25:200-209.
12. Lendon CI, Davies MJ, Born GVR, et al. Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis,1991,87:87-90.
13. Biassuci LM, D'Onofrio G, Liuzzo G, et al. Intercellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction but its reduction is not related to ischemia. JAM Coll Cardiol,1996,27:611-616.
14. Virmani R, Kolodgie FD, Burke AP, etal. Lessons from sudden coronary atheirosclerotic lesions. Arterioscler Thromb Vase Biol,2000,20:1262-1275.
15. Libby P. Current concept of the pathogenesis of the cut coronary syndromes. Circulation,2001,104:365.
16. van Der Wal AC, Das PK, Tigges AJ et al. Adhesion modecules on the endothelium and mononuclear cells in human atherosclerotic lesion. Am J Pathol, 1992,141:1427-1433.
17. Jaakkola k, Jalkanen S, Kaunis maki K, et a 1. Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. J Am coll Cardiol,2003,36 (1):122-129.
18. Lewis EJ, Bishop J, Bottomley KM, et al. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitroand in vivo. Br J Pharmacol,1997,121(3):540-546.
19. Orbe J, Fernandez 1, Rodriguez JA. Different expression of MMPs/TIMP-1 in human atherosclerotic lession. Relation to plaque features and vascular bed. Atherosclerosis,2003,170(2):269-276.
20. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis:the good, the bad, and the ugly. Circ Res,2002,90(3):251-262.
21. Kulach A, Dabek J, Glogowska-Ligus J, et al. Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes. Pharmacol Rep,2010,62(6):1108-1116.
22. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
23. Robertson L, Grip L, Mattsson Hulten L, et al. Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention. J Intern Med,2007,262(6):659-667.
24. Shu J, Ren N, Du JB, et al. Increased levels of interleukin-6 and matrix metalloproteinase-9 are of cardiac origin in acute coronary syndrome. Scand Cardiovasc J,2007,41(3):149-154.
25. Silence J, Lupu F, Collen D, et al. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vase Biol,2001,21(9):1440-1445
26. Blankenberg S, Rupp recht HJ, Poirier O, et al. Atherogenesis investigatorsl plasma concentrations and genetic variation of matrixmetalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation,2003,107:1579-1585.
27.赵慧颖,徐宝华,马小欣.血清基质金属蛋白酶活性与动脉粥样硬化斑块稳定性的实验观察.中国微循环,2007,23(9)：1700-1702.
28. De Nooijer R, Verklej CJ, Von der Thusen J H, et al. Lesional over expression of matrixmetalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis. Arterioscler Thromb Vase Bio,2006,26(2): 340-346.
29. Ambrose JA, Martinez EE. A new paradigm for plaque stabilization. Circulation, 2002,105(16):2000-2004.
30. Zhao LQ, Si SY. Advances in research matrix metalloproteinases inhibitiors. Chinese Journal New drugs,2004,13(6):494-497.
31. Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymology:dectection of matrix metalloproteinase activity in vascular tissue. Methodol Commun,1995,9(9):974-980
32. Liu G, Wang B, Zhang J, et al. Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice:Role of downregulation of CD40 and MMP-9 expression. J Ethnopharmacol,2009,126(2):350-354.
33. Kim JY, Kim WJ, Kim H, et al. The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappaB in Macrophages:Implication for Atherosclerosis. Immune Netw,2009,9(3):90-97.
34. Rauch I, Iglseder B, Paulweber B, et al. MMP-9 haplotypes and carotid artery atherosclerosis:an association study introducing a novel multicolour multiplex RealTime PCR protocol. Eur J Clin Invest,2008,38(1):24-33.
35. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
36. Inokubo Y, Hanada H, Ishizaka H, et al. Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome. Am Heat J,2001, 141(2):211-217.
37. Kai H, Ikeda H, Yasukawa H, et al. Peripheral blood levels of matrix metalloproteases-2 and are elevated in patients with acute coronary syndroms. J Am Coll Cardiol,1998,32(2):368-372.
38. Ferroni P, Basill S, Martini F, et al. Serum metalloproteinse 9 levels in patients wirh coronary artery disease:a novel marker of inflammation. J Investig Med,2003, 51(5):295-300.
39. Nomoto K, Oguchi S, Watanade I, et al. Involvement of inflammation in acute coronary syndromes assesses by levels of high-sensitivity protein, matrix metalloproteinase-9 and soluble vadcular-cell adhesion molecule-1. J Cardiol,2003, 42(5):201-206.
40.陈实,周志斌,郭毅,等.血清基质金属蛋白酶-9--脑梗死预后的潜在临床标志物.国外医学脑血管疾病分册,2004,12(4)：260-263.
1. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med,2003,163:205-209.
2. Holmes AL, Burgess HJ, McCulloch K, et al. Day-time cardiac autonomic activity during one week of continuous night shift. J Hum Ergol(Tokyo),2001,30:223-228.
3. Lusardi P, Zoppi A, Preti P, el al. Efects of insuficient sleep on blood pressure in hypertensive patients:a 24-h study. Am J Hypertens,1999,12:63-68.
4. Takase B, Akima T, Satomura K, el al. Efects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother,2004,58:S35-S39.
5. Liu Y, Tanaka H, et al. Overtime work, insufficient sleep, and risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med.2002,59(7): 447-451.
6. Irwin MR, Ziegler M. Sleep deprivation potentiates activation of cardiocascular and catecholamine responses in abstinent alcoholics. Hypertention,2005,45(2): 252-257.
7. Holmes AL, Burgess HJ, Dawson D. Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature. Appl Physiol,2002,92(6): 2578-2584.
8.钟旭,肖毅,黄蓉,等.整夜完全睡眠剥夺对心血管自主神经活动的影响.中华内科杂志,2005,44：577-580.
9.柴慧娟,徐淑梅,杨海贤.睡眠剥夺对人鼠心肌超微结构损伤效应的研究.武警医学,2008,19：24-27.
10.柴慧娟,徐淑梅.睡眠剥夺对人鼠心肌损伤效应和抗氧化指标的影响.中国应用生理学杂志,2008,24：71-75.
11. Kato M, Phillips BG, Sigurdsson G, et al. Effects of sleep deprivation on neural circulatory control. Hypertension,2000,35:1173-1175.
12. Lusardi P, Mugellini A, Preti P, et al. Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects. Am J Hypertens, 1996,9:503-505.
13. Chen HI. Efiects of 30-h sleep loss on cardiorespiratory functions at rest an d in exercise. Med Sci Sports Exere,1991,23:193-198.
14 Vgontzas AN, Mastorakos G, Bixler EO, et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes:potential clinical implications. Clin Endocrinol(Oxf),1999.51:205-215.
15. Tochikubo O, Ikeda A, Miyajima E, et al. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension,1996,27: 1318-1324.
16. Ayas NT, White DP, A1-Delaimy WK, et al. A prospective study of self reported sleep duration and incident diabetes in women. Diabetes Care,2003.26:380-384.
17. Palma BD, Gabriel A JR., Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35:75-79.
18.曹雪亮,苗丹民,皇甫恩,等.高原与平原条件下48h完全睡眠剥夺对血压和心率的影响.解放军预防医学杂志,2003,21：334-336.
19. Perry JC, D'Almeida V, Souza FG, et al. Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats. Respir Physiol Neurobiol,2007,156:250-258.
20. Andersen ML, Martins PJ, D'Almeida V, et al. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp Gerontol,2004,39:817-824.
21. VanHelder T, Symons JD, Radomski MW. Effects of sleep deprivation and exercise on glucose tolerance. Aviat Space Environ Med,1993,64(6):487-492.
22. VanHelder T, Radomski MW. Sleep deprivation and the effect on exercise performance. Sports Med,1989,7(4):235-247.
23. Yeh ET, Willerson JT. Coming of age of C-reactive protein:using inflammation markers in cardiology. Circulation,2003,107(3):370-371.
24. Epstein SE, Zhu J, Najafi AH, et al. Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture. Circulation,2009,119(24):3133-3141.
25. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol,2004, 43(4):678-683.
26.段小莉,王百忍,杨唐斌等.抗CRF单克隆抗体和多克隆抗体的制备及其在睡眠剥夺模型大鼠脑内的变化.细胞与分子免疫学杂志,2005,21：476.
27.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第一军医大学学报,2007,28(2)：201-203.
28. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
29. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
30. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol,2002,80(3):193-197.
31. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
32.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
33. Naidoo N, Giang W,Galante RJ,et al. Sleep deprivation induces the unfolded protein response in muse cerebral cortex. J Neurochem,2005,92 (5):1150-1157.
34.Tononi G, Cirelli C. Modulation of brain gene expression during sleep and wakefulness:a review of recent findings. Neuropsychopharmacology,2001,25: S28-S35.
35.Shaw PJ, Cirelli C, Greenspan RJ et al. Correlates of sleep and waking in Drosophila melanogaster. Science,2000,287:1834-1834.
36.Terao A, Steininger TL, Hyder K, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience,2003,116:187-200.
37. Xu C, Bailly-Maitre B. et al. Endoplasmic reticulum stress:cell life and death decisions. J Clin Invest,2005,115:2656-2664.
38. Thomas RD, Kaufman RJ. A trip to the ER:coping with stress. Trends Cell Biol, 2004,14:20-28.
39. kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest,2002,110:1389-139.
40. Luke Wi seman R, Ralch WE. A new pharmacology-drugging stressed folding pathways. TRENDS in Molecular Medicine,2005,8:347-350.
41. Jung HY, Wek RC. Phosphorylation of the a-Subunit of the Eukaryotic Initiation Factor-2 Reduces Protein Synthesis and Enhances Apoptosis in Response to Proteasome inhibition. The Journal of biological chemistry,2005,14:14189-14202.
42. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling:the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol,2006,38:317.
43.赵忠新,主编.临床睡眠障碍学第一版.上海：第二军医大学出版社,2003：30-710.
44. Simpson N, Dinges DF. Sleep and inflammation. Nutrition Reviews,2007,65(3): 244-252.
45. Hublin C. Parinen M, Koskenvuo M, et al. Sleep and mortality:a population-based 22-year follow-up study. Sleep,2007,30(12):1245-1253.
46. Van Dort CJ. Baghdoyan HA. Lydic R. Adenosine A(1) and A(2A)receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci,2009,29(3):871-881.
47. Altena E, Ramautar JR, Van Der Werf YD, et al. Do sleep complaints contribute to age-related cognitive decline? Prog Brain Res,2010,185:181-205.
48.张亚晶,卢才义,黄亚.睡眠剥夺对大鼠心脏的影响及其致心律失常机制研究.血管康复医学杂志,2009,18(3)：224-226.
1. Szmitko PE, Wang CH, Weisel RD, et al. New markers of inflammation and endothelial cell activation:Part Ⅰ. Circulation.2003,108:1917-1923.
2. O'Leary DH, Polak JF, Wolfson SK Jr. Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Reasearch Group. Stroke,1997,28:348-355.
3.于世勇,黄岚,宋耀明,等.心绞痛患者冠状动脉内皮损伤及意义.中华内科杂志,2003,42：473-475.
4. Hirsch AT. Vascular disease, hypertension, and prevention:"from endothelium to clinical events". J Am Coll Cardiol,2003,42:377-379.
5. Shimokawa H. Primary endothelial dysfunction:atherosclerosis. J Mol Cell Cardiol,1999,31:23-37.
6. Duvall WL. Endothelial Dysfunction and Antioxidants. Mt Sinai J Med,2005,72: 71-80.
7. Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res,2003,93:e17-24.
8. Hamed S, Roguin A. Endothelial progenictor cells and atherosclerosis. Harefuah, 2006,145 (5):358-361,397.
9. Boos CJ, Goon Pk, Lip Gy. Endothelial progentor cells in the vascular pathophysiology of hypertension:arterial stiffness, ageing and more. J Hum Hypertension,2006,20(7):475-477.
10. Lau KK, Chan YH, Yiu KH, et al. Burden of carotid atherosclerosis in patients with stroke:relationships with circulating endothelial progenitor cells and hypertension. J Hum Hyperten,2007,1-7.
11.陈剑飞,黄岚,晋军,等.年龄对骨髓内皮祖细胞功能的影响及意义.四川医学,2006,7(5)：231-233.
12.Suzuki T, Nishida M, Futami S, et al. Neoendothelialization after peripheral blood stem cell transplantation in humans:a case report of a Tokaimura nuclear accident victim. Cardiovasc Res,2003,58:487-492.
13. Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30:967-972.
14. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
15. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
16. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
17. Nikkari ST, O'Brien KD, Ferguson M, et al. Interstitial collagenase in human carotid atherosclerosis. Circulation,1995,92:402-406.
18. Lagrand WK, Niessen HWM, Wolbink GJ, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation,1997, 95:97-103.
19. Cemak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood,1993,82:513-520.
20. Biasucci LM,Liuzzo G, Caligiuri G, et al. Episodic activation of the coagulation system in unstalble angina doses not clicit an acute phase reaction. Am J Cardiol, 1996,77(1):85-87.
21. Torzewski J, Torzewski M, Bowyer DE, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic leisions of human coronary areries. Arterioscler Thromb Vase Biol, 1998,18:1386 1392.
22. Ridker PM. High-sensitivity C-reactive protein:potential adjunct for global risk assessmeatin the primary prevention of cardiovascular disease. Circulation,2001, 103(16):1813-1818.
23. Rifai N, Ridker PM. High sensitivity C-reactive protein:A novel and promising marker of coronary heart disease. Clin Chem,2001,47(3):403-411.
24. Tezono K, Sarker KP, Kikuchi H, et al.Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001,31(2):71-79.
25. Mullenix PS, Andersen CA, Stames BW. Atherosclerosis as inflammation. Ann Vasc Surg,2005,19:130-138.
26. Kanters E, Gijbels MJ, Vergouwe MN, et al. Hematopoietic NF-κB deficiency results in small atherosclerotic lesions with an inflanmlatory phenotype. Blood,2004, 103(3):934-940.
27. Bolick DT, Sfinivasan S, Whetzel A, et al. Lipoxygenase Mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of NF-κB. Arterioscler Thromb Vasc Biol,2006,16(4):16.
28. Rook MF, Neuby AC, Southgate KM. Expression of intercellular adhesion molecules in human saphenous veins:effects of inflammatory cytokines andneointima formation in culture. Atherosclerosis,2000,150(4):33-41.
29. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell,1986,46(5):705-716.
30. Brand K, Page S, Rogler G, et al. Activated transcription factor-kappa B is present in the atherosclerosis lesion. J Clin Invest,1996,97(7):1715-1722.
31. Rodriguez-Porel M, Leman LO, Holmes DR,et al.Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial
32. Sun Juan, Huang YQ. Role of nuclear kappa B signal pathways in process of atherosclerosis. Modem Journal of Integrated Traditional Chinese and Western Medicine,2007,16(15):2158-2162.
33. Ping D, Boekhoudt GH, Rogers EM, et al. Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte Chemoattractant-1 gene. Immunol,1999,162(2):727-734.
34. Menno PJ, De Winther, Edwin Kanters, Georg Kral, et al. Nuclear factor-KB Signaling in Atherogenesis. Arterioscler Thromb Vasc Biol,2005,25:904-914.
35. Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of ciselement "de-coy" against nuclear factor-kB binding site prevents myocardial infaction. NatMed,1997,3(8):894-899.
36. Shin MH, Moon YJ, Seo JE, et al. Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrial electron transport system mediate heat shock2induced MMP-1 and MMP-9 expression. Free Radic Biol Med,2008,44(4): 635-645.
37. Azumi H, Inoue N, Ohashi Y, et al. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris:Important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol,2002,22:1838-1844.
38. Channon KM. Oxidative stress and coronary plaque stability. Arterioscler Thromb Vasc Biol,2002,22:1751-1752.
39. Steinberg D. Low density lipoprotein oxidation its pathobiological significance. J Biol Chem,1997,272(34):20963-20966.
40. Cominacini L, Ulisse G, Pasini AF, et al. Antioxidants inhibit the expression of intercellular cell adhension molecula-1 and vascular cell adhension molecule-1 induced by oxidized LDL on human umbilical endothelial cells. Free Radic Biol Med, 1997,22(1-2):117-127.
41. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res.1999; 85(8):753-766.
42. Lawrence de Koning AB, Werstuck GH, Zhou J, et al. Hyper homocysteinemia and its role in the evelopment of artherosclerosis. Clin Biochen,2003,36(6):431.
43. Galis ZS, Muszynski M, Sukhova GK, et al. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci,1995,748:501-507.
44. Lewis EJ, Bishop J, Bottomley KM, et al. Ro32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitroand in vivo. Br J Pharmacol,1997,121(3):540-546.
45. Orbe J, Fernandez 1, Rodriguez JA. Different expression of MMPs/TIMP-1 in human atherosclerotic lession. Relation to plaque features and vascular bed. Atherosclerosis,2003,170(2):269-276.
46. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis:the good, the bad, and the ugly. Circ Res,2002,90(3):251-262.
47. Kulach A, Dabek J, Glogowska-Ligus J, et al. Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes. Pharmacol Rep,2010,62(6):1108-1116.
48. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
49. Robertson L, Grip L, Mattsson Hulten L, et al. Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention. J Intern Med,2007,262(6):659-667.
50. Shu J, Ren N, Du JB, et al. Increased levels of interleukin-6 and matrix metalloproteinase-9 are of cardiac origin in acute coronary syndrome. Scand Cardiovasc J,2007,41(3):149-154.
51. Silence J, Lupu F, Collen D, et al. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol,2001,21(9):1440-1445
52. Blankenberg S, Rupp recht HJ, Poirier O, et al. Atherogenesis investigators 1 plasma concentrations and genetic variation of matrixmetalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation,2003,107:1579-1585.
53.赵慧颖,徐宝华,马小欣.血清基质金属蛋白酶活性与动脉粥样硬化斑块稳定性的实验观察.中国微循环,2007,23(9)：1700-1702.
54. De Nooijer R, Verklej CJ, Von der Thusen J H, et al. Lesional over expression of matrixmetalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis. Arterioscler Thromb Vase Bio,2006,26(2): 340-346.
55. Ambrose JA, Martinez EE. A new paradigm for plaque stabilization. Circulation, 2002,105(16):2000-2004.
56. Zhao LQ, Si SY. Advances in research matrix metalloproteinases inhibitiors. Chinese Journal New drugs,2004,13(6):494-497.
57. Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymology:dectection of matrix metalloproteinase activity in vascular tissue. Methodol Commun,1995,9(9):974-980
58. Liu G, Wang B, Zhang J, et al. Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice:Role of downregulation of CD40 and MMP-9 expression. J Ethnopharmacol,2009,126(2):350-354.
59. Kim JY, Kim WJ, Kim H, et al. The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappa B in Macrophages:Implication for Atherosclerosis. Immune Netw,2009,9(3):90-97.
60. Rauch I, Iglseder B, Paulweber B, et al. MMP-9 haplotypes and carotid artery atherosclerosis:an association study introducing a novel multicolour multiplex RealTime PCR protocol. Eur J Clin Invest,2008,38(1):24-33.
61. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
62. Rajagopalan S, Meng XP, Ramasamy S, et al. Reactive oxygen species p reduced bymacrophage-derived foam cells regulate the activity of vascularmatrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest,1996,98:2572-2579.
63. Braunwald E. Shattuck Lecture-Cardiovascular medicine at the turn of the millennium:triumphs concerns and opportunities. N Engl J Med,1997,337: 1360-1369.
2. Benington JH, Heller HC. Does the function of REM sleep concern non-REM sleep or waking? Prog Neurobiol.1994,44(5):433-449.
3.赵忠新,主编.临床睡眠障碍学.第一版.上海：第二军医大学出版社,2003：30-710.
4. Simpson N, Dinges DF. Sleep and inflammation. Nutrition Reviews,2007,65(3): 244-252.
5. Hublin C. Parinen M, Koskenvuo M, et al. Sleep and mortality:a population-based 22-year follow-up study. Sleep,2007,30(12):1245-1253.
6. Van Dort CJ. Baghdoyan HA. Lydic R. Adenosine A(1) and A(2A)receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci,2009,29(3):871-881
7. Altena E, Ramautar JR, Van Der Werf YD, et al. Do sleep complaints contribute to age-related cognitive decline? Prog Brain Res.2010,185:181-205.
8.张亚晶,卢才义,黄亚.睡眠剥夺对大鼠心脏的影响及其致心律失常机制研究.血管康复医学杂志,2009,18(3),224-226.
9. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Me d,2003,163:205-209.
10. Holmes AL, Burgess HJ, McCulloch K, et al. Day-time cardiac autonomic activity during one week of continuous night shift. J Hum Ergol(Tokyo),2001,30: 223-228.
11. Lusardi P, Zoppi A, Preti P, el al. Efects of insuficient sleep on blood pressure in hypertensive patients:a 24-h study. Am J Hypertens,1999,12:63-68.
12. Takase B, Akima T, Satomura K, el al. Efects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother,2004,58:S35-S39.
13. Liu Y, Tanaka H, et al. Overtime work, insufficient sleep, and risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med.2002,59(7): 447-451.
14. Irwin MR, Ziegler M. Sleep deprivation potentiates activation of cardiocascular and catecholamine responses in abstinent alcoholics. Hypertention.2005,45(2): 252-257.
15. Holmes AL, Burgess HJ, Dawson D. Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature. Appl Physiol.2002,92(6): 2578-2584.
16.钟旭,肖毅,黄蓉,等.整夜完全睡眠剥夺对心血管自主神经活动的影响.中华内科杂志,2005,44：577-580.
17.柴慧娟,徐淑梅,杨海贤.睡眠剥夺对人鼠心肌超微结构损伤效应的研究.武警医学,2008,19：24-27.
18.柴慧娟,徐淑梅.睡眠剥夺对人鼠心肌损伤效应和抗氧化指标的影响.中国应用生理学杂志,2008,24：71-75.
19. Kato M, Phillips BG, Sigurdsson G, et al. Effects of sleep deprivation on neural circulatory control. Hypertension,2000,35:1173-1175.
20. Lusardi P, Mugellini A, Preti P, et al. Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects. Am J Hypertens, 1996,9:503-505.
21. Chen HI. Efiects of 30-h sleep loss on cardiorespiratory functions at rest an d in exercise. Med Sci Sports Exere,1991,23:193-198.
22 Vgontzas AN, Mastorakos G, Bixler EO, et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes:potential clinical implications. Clin Endocrinol(Oxf),1999.51:205-215.
23. Tochikubo O, Ikeda A, Miyajima E, et al. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension,1996,27: 1318-1324.
24. Ayas NT, White DP, Al-Delaimy WK, et al. A prospective study of self reported sleep duration and incident diabetes in women. Diabetes Care.2003.26:380-384.
25. Palma BD, Gabriel A JR, Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35:75-79.
26.曹雪亮,苗丹民,皇甫恩,等.高原与平原条件下48h完全睡眠剥夺对血压和心率的影响.解放军预防医学杂志,2003,21：334-336.
27. Perry JC, D'Almeida V, Souza FG, et al. Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats. Respir Physiol Neurobiol,2007,156:250-258.
28. Andersen ML, Martins PJ, D'Almeida V, et al. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp Gerontol,2004,39:817-824.
29. VanHelder T, Symons JD, Radomski MW. Effects of sleep deprivation and exercise on glucose tolerance. Aviat Space Environ Med,1993,64(6):487-492.
30. VanHelder T, Radomski MW. Sleep deprivation and the effect on exercise performance. Sports Med,1989,7(4):235-247.
31. Yeh ET, Willerson JT. Coming of age of C-reactive protein:using inflammation markers in cardiology. Circulation.2003,107(3):370-371.
32. Epstein SE, Zhu J, Najafi AH, et al. Insights into the role of infection in atherogenesis and in plaque rupture. Circulation,2009,119(24):3133-3141.
33. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol.2004, 43(4):678-683.
34.段小莉,王百忍,杨唐斌等.抗CRF单克隆抗体和多克隆抗体的制备及其在睡眠剥夺模型大鼠脑内的变化.细胞与分子免疫学杂志,2005,21：476.
35.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第一军医大学学报,2007,28(2)：201-203.
36. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
37. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
38. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol.2002,80(3):193-197.
39. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol.1995, 50(10):1557-1565.
40.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
41. Naidoo N, Giang W, Galante RJ,et al. Sleep deprivation induces the unfolded protein response in muse cerebral cortex. J Neurochem.2005,92 (5):1150-1157.
42. Tononi G, Cirelli C. Modulation of brain gene expression during sleep and wakefulness:a review of recent indings. Neuropsychopharmacology.2001,25: S28-S35.
43. Shaw PJ, Cirelli C, Greenspan RJ et al. Correlates of sleep and waking in Drosophila melanogaster. Science.2000,287:1834-1834.
44. Terao A, Steininger TL, Hyder K, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience.2003,116:187-200.
45. Xu C, Bailly-Maitre B. et al. Endoplasmic reticulum stress:cell life and death decisions J. Clin. Invest.2005,115:2656-2664.
46. Thomas RD, Kaufman RJ. A trip to the ER:coping with stress. Trends Cell Biol. 2004,14:20-28.
47. kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest,2002,110:1389-139.
48. Luke Wi, seman R, Ralch WE. A new pharmacology-drugging stressed folding pathways. TRENDS in Molecular Medicine,2005,8:347-350.
49. Jung HY, Wek RC. Phosphorylation of the a-subunit of the eukaryotic initiation factor-2 reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. The Journal of biological chemistry,2005,14:14189-14202.
50. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling:the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol,2006,38:317.
51. Glass ck, Witztum JL. Atherosclerosis, the road ahead. Cell,2001,104:503.
52. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
53. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
54. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
55. Nikkari ST, O'Brien KD, Ferguson M, et al. Interstitial collagenase (MMP-1) in human carotid atherosclerosis. Circulation,1995,92:1393-1398.
56. Empana JP, Jouven X, Canoui-Poitrine F, et al. C-Reactive protein, interleukin 6, fibrinogen and risk of sudden death in european middle-aged men:the PRIME study. Arterioscler Thromb Vasc Biol,2010,30(10):2047-2052.
57. Wassel CL, Barrett-Connor E, Laughlin GA. Association of circulating C-reactive protein and interleukin-6 with longevity into the 80s and 90s:the rancho bernado study. J Clin Endocrinol Metab,2010,95(10):4748-4755.
58. Hamer M, Chida Y, Stamatakis E. Association of very highly elevated C-reactive protein concentration with cardiovascular events and all-cause mortality. Clin Chem, 2010,56(1):132-135.
59. Elkind MSV. Inflammatory mechanisms of stroke. Stroke suppl,2010,41(10): S3-S8.
60. Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality:an individual participant meta-analysis. Lancet.2010,375(9709):132-140.
61. Lagrand WK. Niessen HW. Wblbink GJ, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation, 1997,95:97-103.
62.温先勇,杭永伦,薜莉等.冠心病患者C-反应蛋白、一氧化氮、白细胞介素-6测定的临床意义.中国现代医学杂志,2003,13(1)：69-70.
63. Tezono K, Sarker KP, Kikuchi H, et al. Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001;31(2):71-79.
64. Mullenix PS, Andersen CA, Stames BW. Atherosclerosis as inflammation. Ann Vase Surg,2005,19(1):130-138.
65. Shin MH, Moon YJ, Seo JE, et al. Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression. Free Radic BiolMed,2008,44(4): 635-645.
66. Azumi H, Inoue N, Ohashi Y, et al. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris:Important role of NAD(P)H oxidase. Arterioscler Thromb Vase Biol,2002,22:1838-1844.
67. Channon KM. Oxidative stress and coronary plaque stability. Arterioscler Thromb Vase Biol,2002,22:1751-1752.
68. Steinberg D. Low density lipoprotein oxidation its pathobiological significance. J Biol Chem,1997,272(34):20963-20966.
69. Cominacini L, Ulisse G, Pasini AF, et al. Antioxidants inhibit the expression of intercellular cell adhension molecula-1 and vascular cell adhension molecule-1 induced by oxidized LDL on human umbilical endothelial cells. Free Radic Biol Med, 1997,22(1-2):117-127.
70. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res,1999,85(8):753-766.
71. Lawrence de Koning AB, Werstuck GH, Zhou J, et al. Hyper homocysteinemia and its role in the evelopment of artherosclerosis. Clin Biochen,2003,36(6):431.
72. Galis ZS, Muszynski M, Sukhova GK, et al. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci.1995,748:501-507.
73. Rajagopalan S, Meng XP, Ramasamy S, et al. Reactive oxygen species p reduced bymacrophage-derived foam cells regulate the activity of vascularmatrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest,1996,98:2572-2579.
74. Braunwald E. Shattuck Lecture-cardiovascular medicine at the turn of the millennium:triumphs concerns and opportunities. N Engl J Med,1997,337: 1360-1369.
1. Youngblood BD, Zhou J, Smagin GN, et al. Sleep deprivation by the "flower pot" technique and spatial reference memory. Physiol Behav.1997,61(2):249-56.
2.王园园,龙民慧,邹民吉,等.大鼠动脉粥样硬化动物模型的建立和评价.中国实验动物学报,2008,16(6)：421-423.
3.杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立.第二军医大学学报,2003,24(7)：802-804.
4.刘磊,焦向英,张炜芳,等.高脂饲料及维生素D3联合应用建立大鼠动脉粥样硬化模型.山西医科大学学报,2005,36(6)：681-683.
5. Palma BD, Gabriel AJr, Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35(1):75-79.
6. Dou W, Zhao ZX, Miao MY, et al. The effect of sleep deprivation on cognitive and cerebral mitochondrial repiratory function in rats. Neuroscience Bulletin,2005,21(3): 204-209.
7. Suchecki D, Tufik S. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Bchav,2000,68 (3):309-316.
8.黄建欧,赵忠新.大鼠睡眠剥夺方法的研究进展.中华神经医学杂志,2004,3(3)：229-231.
9. Bennani-Kabchi N, Kehel L, EI Bouayadi F, et al. New model of atherosclerosis in insulin resistant sand rats:hypercholesterolemia combined with D2 vitamin. Atherosclerosis,2000,150(1):55-61.
10.沈丽,卢维晨,姚俊宇,等.不同方法建立动脉粥样硬化大鼠模型的比较.心脏杂志,2005,17(1)：18-20.
11.温进坤,韩梅,杜玮南.一种快速建立大鼠动脉粥样硬化模型的实验方法.中国老年学杂志,2001,21,50-52.
12.杨鹏远,丙耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立.第二军医大学学报,2003,24(7)：802-804.
13.郭延松,吴宗贵,杨军柯,等.三种大鼠动脉粥样硬化模型复制方法的比较.中国动脉粥样硬化杂志,2003,11(5)：465-469.
14. Schwierin B, Borbeley AA, Tobler I, et al. Effects of N6-cyclopentyladenosine and caffeine on sleep regulation in the rat. Eur J Pharmacol,1996,300:163-171.
15. Gonzalez MM, Valatx J L, Debilly G Role of the locus coeruleus in the sleep rebound following two different sleep deprivation methods in the rat. Brain-Res,1996, 740(1-2):215-226.
16. Charifi C, Paut-Pagano L, Debilly G, et al. Effect of noradrenergic denervation of the amygdala upon recovery after sleep deprivation in the rat. Neurosci-Let,2000, 287(1):41-44.
17. Deborah Suchecki, Sergio Tufik. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiology& Behavior,2000,68:309-316.
18.吴兴曲,杨来启.睡眠剥夺对大鼠学习能力的影响及机制初步研究.解放军预防医学杂志,2002,20(4)：241-243.
19.刘长云,王海明,陈坚,等.大鼠睡眠剥夺后行为及丘脑诱生型一氧化氮合酶mRNA表达的变化.第二军医大学学报,2002,23(3)：281-283.
20. Taylor LR, Costanzo DJ. Social dominance, adrenal weight, and the reticuloendothelial system in rats. Behav Biol,1975,13:167-174.
21. Suchecki D, Hipo lide DC, Lobo LL, et al. ACTH and corticosterone responses to multiple and single platform techniques-induced REM sleep deprivation. Sleep Research,1995,24:455.
22. Nunes Jr G, Tufik S. Validation of modified multiple platform methods (MPM) of paradoxical sleep deprivation in rats. Sleep Research,1994,23:419.
23.刘永学,高月.应激研究进展.中国病理生理杂志,2002,18：218-221.
24. Taheri S, Lin L, Austin D, et al. Short sleep duration is associated with reduced leptin, elecated ghrelin, and increased body mass index. PLoS Med,2004,1(3): 62-79.
25.孙慧,姚明辉.睡眠不足及夺眠引起机体生理功能的变化.世界临床药物,2009,30(4)：233-236.
26.姚泰主编.生理学5版.北京：人民卫生出版社,2003,398-399.
27.刘卫,钱令嘉,杨志华,等.慢性温和应激抑郁模型大鼠5-羟色胺、色氨酸和应激激素的变化.中国应用生理学杂志,2006,22(2)：169-172.
28.胡淑芳,王惠利,杨来启,等.急性高原应激大鼠脑组织NO, SOD及血浆皮质醇的含量变化.中国心理卫生杂志,2002,16(8)：518-519.
29.周爱军,罗海吉,卢晓翠,等.L-精氨酸对热应激大鼠血清皮质醇变化的影响.中国公共卫生,2005,21(5)：594-595.
30.杨惠芳,张银娥,刘秀芳等.慢性心理应激对大鼠行为及血清皮质醇影响及运动的调节作用.工业卫生与职业病,2008,34(3)：133-136.
31.季乃军,方宗桥,王成尧,等.原发性高血压患者血清皮质醇测定及其临床意义.河北医学,1995,1(5)：295-297.
32.程志平.内分泌生理学.北京：人民卫生出版社,1984：193.
33.吴淑杰,张雪峰,许丽华,等.高血压和冠心病患者的血清皮质醇浓度测定.吉林医学院学报,1996,16(4)：28-29.
34.吴木潮,黄宾协,黎锋,等.代谢综合征患者血清和尿皮质醇水平与心血管危险因素的关系.广东医学.2006,27(2)：206-207.
35.李丛丛.怒志对冠心病心绞痛患者神经-内分泌-免疫机制的研究.山东：山东中医药大学.2008：16.
36.刘雁峰,王天芳,杨维益,等.复合应激因素致大鼠促肾上腺皮质激素和皮质酮含量变化的研究.中国医药学报.2000,15(1)：72-73.
37.王莹,杨祖铭,朱海娟,等.外源性褪黑素对缺氧缺血性脑损伤新生大鼠血浆促肾上腺皮质激素和皮质酮的影响.实用儿科临床杂志,2008,23：430-432.
38. Choi DC, Evanson NK, Furay AR, et al. The anteroventral bed nucleus of the stria terminalis differentially regulates hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Endocrinology,2008,149(2):818-26.
1. Everson CA, Wehr TA. Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat. Am J Physiol.1993,264(2):376-387.
2. Droge W. Free radicals in t he physiological control of cell function. Physiol Rev, 2002,82:47-95.
3. Murrant CL, Reid MB. Detection of reactive oxygen and reactive nitrogen species in skeletal muscle. Microsc Res Tech,2001,55:236-248.
4. Schulz JB, Lindenau J, Seyfried J, et al. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem,2000,267:4904-4911.
5. Ran Q T, Liang HY, Gu MJ, et al. Transgenic mice over expressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem, 2004,279:55137-55146.
6. Bergamini CM, Gambetti S, Dondi A, et al. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des.2004,10(14):1611-1626.
7. Bauer V, Bauer F. Reactive oxygen species as mediators of tissue protection and injury. Gen Physiol Biophys.1999,18:7-14.
8.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第二军医大学学报.2007,28(2)：201-203.
9. Chang HM, Mai FD, Chen BJ, et al. Sleep deprivation predisposes liver to oxidative stress and phospholipid damage:a quantitative molecular imaging study. J Anat,2008,212(3):295-305.
10. Kumar A, Singh A. Possible involvement of GABA ergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice. Fundam Clin Pharmacol,2009,23(4):439-448.
11. Findrik Z, Vrsalovic Presecki A, Vasic Racki D. Mathematical modelling of NADH oxidation catalyzed by new NADH oxidase from Lactobacillus brevis in continuously operated enzyme membrane reactor. J Biosci Bioeng,2007,104 (4): 275-280.
12.朱秉匡,钟毅,郑仕富,等.益寿调脂片调脂和抗自由基损伤的研究.广州中医药大学学报,1999,16(1)：13-16.
13.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
14. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
15. Abilio VC, Vera JA Jr, Ferreira LS, et al. Effects of melatonin on orofacial movements in rats. Psychopharmacology (Berl),2002,161(4):340-347.
16. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
17. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
18. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol,2002,80(3):193-197.
19. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
20. Kalonia H, Bishnoi M, Kumar A. Possible mechanism involved in sleep deprivation-induced memory dysfunction. Methods Find Exp Clin Pharmacol,2008, 30(7):529-535.
21. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol,2005,25 (1):29-38.
22. Papaharalambus CA, Griendling KK. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med,2007,17(2): 48-54.
23. Armando R, Hector F, Lamberto R, et al. Oxidative Stress at the VascularWall. Mechanistic and Pharmacological Aspects. Archives of Medical Research,2006, (37): 436-448.
24. Chappell DC, Varner SE, Nerem RM, et al. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res,1998,82 (5): 532-539.
25. Galis ZS, Asanuma K, Godin D, et al. Nacetylcysteine decreases the matrix-degrading capacity of macrophage - derived foamcells:new target for antioxidant therapy? Circulation,1998,97(24):2445-2453.
1.芮耀诚.抗动脉粥样硬化药物的研究进展.国外医学：药学分册.1995,22：257-261.
2. Ross R. Atherosclerosis-an inflammatory disease. N Engl Med,1999,340 (2): 115-126.
3. Laurila A, Bloigu A, Nayha SI. Association of helicobacter pylori infection with elevated serum lipids. Atherosclerosis,1999,142(11):207-210.
4.汤耀法.光密度的由来及其物理意义.中国医学物理学杂,1997,14(3)：179-181.
5. Tung A, Herrera S, Bergmann BW, eL al. Can recovery from sleep deprivation occur during general anesthesia. Sleep,2003.26(12):1448.
6. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immunemediated inflammation. N Engl J Med,1995,332:1351-1362.
7. McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med, 1998,338:171-179.
8.Turk Rhen, John A, Cidlowski. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med,2005,353:1711-1723.
9. Nels on LE, Lu J, Guo T, et al. The alpha2-adenocepteragonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology,2003,98(4):428.
10. Tanase D, Baghdoyan HA, Lydic R. Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time. Anesthesiology,2003,98(6):912.
11. Meier-Ewert HK. Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol,2004,43: 678-683.
12. Irwin MR, Wang M, Campomayor CO, et al. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med, 2006,166:1756-1762.
13. Prey DJ, Fleshner M, Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun, 2007,21:1050-1057.
14. Munro JM, Cotran RS. The pathogenesis of atherosclerosis:atherogenesis and inflammation. Lab Invest,1988,58(3):249-619.
15. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
16. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
17. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
18.李巧汶.炎症与组织因子在冠心病中的研究进展.心血管病学进展,2008,29(1)：61-63.
19. Mullenix PS, Andersen CA, Starnes BW. Atherosclerosis as inflammation. Ann Vase Surg,2005,19(1):130-138.
20. Koenig W, Khuseyinova N, Baumert J, et al. Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women:results from the MONICA/KORA Augsburg case-cohort study,1984-2002. Arterioscler Thromb Vasc Biol,2006,26(12): 2745-2751.
21. Hamer M, Chida Y, Stamatakis E. Association of very highly elevated C-reactive protein concentration with cardiovascular events and all-cause mortality. Clin Chem, 2010,56(1):132-135.
22. Elkind MSV. Inflammatory Mechanisms of Stroke. Stroke suppl,2010,41(10): S3-S8.
23. Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality:an individual participant meta-analysis. Lancet,2010,375(9709):132-140.
24. Jarvisalo M, Harmoinen A, Hakanen M, et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol, 2002,22:1323-1328.
25. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease:application to clinical and public health practice:Astatement for health care professionals from the Centers for Disease Control and Prevention and the American HeartAssociation. Circulation,2003,107(3):499-511.
26. Cushman M, Arnold AM, Psaty BM, et al. C-reactive protein and the 10-year incidence of coronary heart disease in older men and women. Circulation,2005,112: 25-31.
27. Koenig W, Lowel H, Baumert J, et al. C-reactive protein modulates risk prediction based on the Framingham Score:implications for future risk assessment: results from a large cohort study in southern Germany. Circulation,2004,109(11): 1349-1353.
28.崔健昆,那坤.C反应蛋白与冠心病的相关性的研究.世界中西医结合杂志, 2010,5(1)：70.
29. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease:application to clinical and public health practice:Astatement for health care professionals from the centers for disease control and prevention and the american heart association. Circulation,2003,107(3):499-511.
30. Tezono K, Sarker KP, Kikuchi H, et al. Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001; 31(2):71-79.
31. Funayama H, Ishikawa SE, Kubo N, et al. Increases in interleukin-6 and matrix metalloproteinase-9 in the infarct-related coronary artery of acute myocardial infarction. Circ J,2004,68(5):451-454.
32. Szekanecz Z, Kerekes G, Der H, et al. Accelerated atherosclerosis in rheumatoid arthritis. Ann N YAcad Sci,2007,1108:349-358.
33.王育珊,王骥,王广.急险心肌梗死患者缺血-再灌注过程中血清白细胞介素-6,白细胞介素-8的动态变化及意义.中华心血管病杂志,2004,32：1.
34. Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis:a comprehensive review of studies in mice. Cardiovasc Res,2008,79(3):360-376.
35. Petrovay F, Heltai K, Kis Z, et al. Chronic infections and histamine, CRP and IL-6 levels after percutaneous trans luminal coronary angioplasty. Inflamm Res,2007, 56(9):362-367.
36. Mysliwska J, Wieckiewicz J, Hak L, et al. Interleukin 6 polymorphism corresponds to the number of severely stenosed coronary arteries. Eur Cytokine Netw, 2006,17(3):181-188.
37.洪永敦,黄衍寿,吴辉,等.冠心病中医证候与炎症因子关系的临床研究.广州中医药大学学报,2005,22(2)：81-86.
38. Kanters E, Gijbels MJ, Vergouwe MN, et al. Hematopoietic NF-κB deficiency results in small atherosclerotic lesions with an inflanmlatory phenotype. Blood,2004, 103(3):934-940.
39. Bolick DT, Sfinivasan S, Whetzel A, et al. Lipoxygenase Mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of NF-κB. Arterioscler Thromb Vasc Biol,2006,16(4):16.
40. Rook MF, Neuby AC, Southgate KM. Expression of intercellular adhesion molecules in human saphenous veins:effects of inflammatory cytokines andneointima formation in culture. Atherosclcrosis,2000,150(4):33-41.
41. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell,1986,46(5):705-716.
42. Brand K, Page S, Rogler G, et al. Activated transcription factor-kappa B is present in the atherosclerosis lesion. J Clin Invest,1996,97(7):1715-1722.
43. Rodriguez-Porel M, Leman LO, Holmes DR, et al. Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial function in hypercholesterolemic pigs. Cardiovasc Res,2002,53: 1010-1018.
44. Sun Juan, Huang YQ. Role of nuclear kappa B signal pathways in process of atherosclerosis. Modem Journal of Integrated Traditional Chinese and Western Medicine,2007,16(15):2158-2162.
45. Ping D, Boekhoudt GH, Rogers EM, et al. Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte Chemoattractant-1 gene. Immunol,1999,162(2):727-734.
46. Menno PJ, De Winther, Edwin Kanters, Georg Kral, et al. Nuclear factor-KB Signaling in Atherogenesis. Arterioscler Thromb Vasc Biol,2005,25:904-914.
47. Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of ciselement "de-coy" against nuclear factor-KB binding site prevents myocardial infaction. Nat Med,1997,3(8):894-899.
48. Calabro P, Cirillo P, Limongelli G,et al. Tissue factor is induced by resistin in human coronary artery endothelial cells by the NF-KB-dependent pathway. J Vasc Res, 2011,48(1):59-66.
49. Real JT, Martinez-Hervas S, Garcia-Garcia AB, et al. Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia. Eur J Clin Invest,2010,40(2):89-94.
50. Sanchez-Galan E, G6mez-Hernandez A, Vidal C, et al. Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis. Cardiovasc Res.2009,81(1):216-225
1. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient. A call for new definition and risk assessment strategies:part I and part Ⅱ. Circulation, 2003,108:1664-1778.
2.胡大一.急性冠状动脉综合征的治疗新对策和新模式.中国介入心脏病学杂志,2002,10(1)：3.
3. Loftμs IM, Naylor AR, Goodall S. Increased matrixmetalloproteinases-9 activity in unstable carotid plaque. A potential role on acute plaque disruption. Stroke,2003,31 (1):40-47.
4. Funayama H, Ishikawa SE, Kubo N, et al. Increases in interleukin-6 and matrix metallop roteinases-9 in the infarct-related coronary artery of acute myocardial infarction. Circ J,2004,68(5):451-454.
5. ManginasA, Bei E, Chaidaroglou A, et al. Peripheral level of matrixmetalloproteinases-9, interleukin-6 and C-reactive protein are elevated in patients with acute coronary syndromes:correlations with serum troponin I. Clin Cardiol,2005,28(4):182-186.
6. Berul CI, Aronovitz MJ, Wang PJ, et al. In vivo cardiac electrophysiology studies in the mouse. Circulation,1996,94(10):2641-2648.
7.施新酞,等.医学动物实验方法.北京：人民卫生出版社,1979：304.
8.徐叔云,卞如濂,陈修等.药理实验方法学,第三版.北京：人民卫生出版社,2002：1007-1013.
9. Stamler JS, Goldman ME, Gomes J,et al. The effect of stress and fatigue on cardiac rhythm in medical interns. J Electrocardiol.1992,25(4):333-338.
10. Bolli R, Oxygen-derived free radicals and myocardial reperfusion injury:an overview. Cardiovasc Drugs Ther,1991,5(Suppl 2):249-268.
11. Kerr ME, Bender CM, Monti EJ. An introduction to oxygen free radicals. Heart Lung,1996,25:200-209.
12. Lendon CI, Davies MJ, Born GVR, et al. Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis,1991,87:87-90.
13. Biassuci LM, D'Onofrio G, Liuzzo G, et al. Intercellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction but its reduction is not related to ischemia. JAM Coll Cardiol,1996,27:611-616.
14. Virmani R, Kolodgie FD, Burke AP, etal. Lessons from sudden coronary atheirosclerotic lesions. Arterioscler Thromb Vase Biol,2000,20:1262-1275.
15. Libby P. Current concept of the pathogenesis of the cut coronary syndromes. Circulation,2001,104:365.
16. van Der Wal AC, Das PK, Tigges AJ et al. Adhesion modecules on the endothelium and mononuclear cells in human atherosclerotic lesion. Am J Pathol, 1992,141:1427-1433.
17. Jaakkola k, Jalkanen S, Kaunis maki K, et a 1. Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. J Am coll Cardiol,2003,36 (1):122-129.
18. Lewis EJ, Bishop J, Bottomley KM, et al. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitroand in vivo. Br J Pharmacol,1997,121(3):540-546.
19. Orbe J, Fernandez 1, Rodriguez JA. Different expression of MMPs/TIMP-1 in human atherosclerotic lession. Relation to plaque features and vascular bed. Atherosclerosis,2003,170(2):269-276.
20. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis:the good, the bad, and the ugly. Circ Res,2002,90(3):251-262.
21. Kulach A, Dabek J, Glogowska-Ligus J, et al. Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes. Pharmacol Rep,2010,62(6):1108-1116.
22. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
23. Robertson L, Grip L, Mattsson Hulten L, et al. Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention. J Intern Med,2007,262(6):659-667.
24. Shu J, Ren N, Du JB, et al. Increased levels of interleukin-6 and matrix metalloproteinase-9 are of cardiac origin in acute coronary syndrome. Scand Cardiovasc J,2007,41(3):149-154.
25. Silence J, Lupu F, Collen D, et al. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vase Biol,2001,21(9):1440-1445
26. Blankenberg S, Rupp recht HJ, Poirier O, et al. Atherogenesis investigatorsl plasma concentrations and genetic variation of matrixmetalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation,2003,107:1579-1585.
27.赵慧颖,徐宝华,马小欣.血清基质金属蛋白酶活性与动脉粥样硬化斑块稳定性的实验观察.中国微循环,2007,23(9)：1700-1702.
28. De Nooijer R, Verklej CJ, Von der Thusen J H, et al. Lesional over expression of matrixmetalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis. Arterioscler Thromb Vase Bio,2006,26(2): 340-346.
29. Ambrose JA, Martinez EE. A new paradigm for plaque stabilization. Circulation, 2002,105(16):2000-2004.
30. Zhao LQ, Si SY. Advances in research matrix metalloproteinases inhibitiors. Chinese Journal New drugs,2004,13(6):494-497.
31. Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymology:dectection of matrix metalloproteinase activity in vascular tissue. Methodol Commun,1995,9(9):974-980
32. Liu G, Wang B, Zhang J, et al. Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice:Role of downregulation of CD40 and MMP-9 expression. J Ethnopharmacol,2009,126(2):350-354.
33. Kim JY, Kim WJ, Kim H, et al. The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappaB in Macrophages:Implication for Atherosclerosis. Immune Netw,2009,9(3):90-97.
34. Rauch I, Iglseder B, Paulweber B, et al. MMP-9 haplotypes and carotid artery atherosclerosis:an association study introducing a novel multicolour multiplex RealTime PCR protocol. Eur J Clin Invest,2008,38(1):24-33.
35. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
36. Inokubo Y, Hanada H, Ishizaka H, et al. Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome. Am Heat J,2001, 141(2):211-217.
37. Kai H, Ikeda H, Yasukawa H, et al. Peripheral blood levels of matrix metalloproteases-2 and are elevated in patients with acute coronary syndroms. J Am Coll Cardiol,1998,32(2):368-372.
38. Ferroni P, Basill S, Martini F, et al. Serum metalloproteinse 9 levels in patients wirh coronary artery disease:a novel marker of inflammation. J Investig Med,2003, 51(5):295-300.
39. Nomoto K, Oguchi S, Watanade I, et al. Involvement of inflammation in acute coronary syndromes assesses by levels of high-sensitivity protein, matrix metalloproteinase-9 and soluble vadcular-cell adhesion molecule-1. J Cardiol,2003, 42(5):201-206.
40.陈实,周志斌,郭毅,等.血清基质金属蛋白酶-9--脑梗死预后的潜在临床标志物.国外医学脑血管疾病分册,2004,12(4)：260-263.
1. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med,2003,163:205-209.
2. Holmes AL, Burgess HJ, McCulloch K, et al. Day-time cardiac autonomic activity during one week of continuous night shift. J Hum Ergol(Tokyo),2001,30:223-228.
3. Lusardi P, Zoppi A, Preti P, el al. Efects of insuficient sleep on blood pressure in hypertensive patients:a 24-h study. Am J Hypertens,1999,12:63-68.
4. Takase B, Akima T, Satomura K, el al. Efects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother,2004,58:S35-S39.
5. Liu Y, Tanaka H, et al. Overtime work, insufficient sleep, and risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med.2002,59(7): 447-451.
6. Irwin MR, Ziegler M. Sleep deprivation potentiates activation of cardiocascular and catecholamine responses in abstinent alcoholics. Hypertention,2005,45(2): 252-257.
7. Holmes AL, Burgess HJ, Dawson D. Effects of sleep pressure on endogenous cardiac autonomic activity and body temperature. Appl Physiol,2002,92(6): 2578-2584.
8.钟旭,肖毅,黄蓉,等.整夜完全睡眠剥夺对心血管自主神经活动的影响.中华内科杂志,2005,44：577-580.
9.柴慧娟,徐淑梅,杨海贤.睡眠剥夺对人鼠心肌超微结构损伤效应的研究.武警医学,2008,19：24-27.
10.柴慧娟,徐淑梅.睡眠剥夺对人鼠心肌损伤效应和抗氧化指标的影响.中国应用生理学杂志,2008,24：71-75.
11. Kato M, Phillips BG, Sigurdsson G, et al. Effects of sleep deprivation on neural circulatory control. Hypertension,2000,35:1173-1175.
12. Lusardi P, Mugellini A, Preti P, et al. Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects. Am J Hypertens, 1996,9:503-505.
13. Chen HI. Efiects of 30-h sleep loss on cardiorespiratory functions at rest an d in exercise. Med Sci Sports Exere,1991,23:193-198.
14 Vgontzas AN, Mastorakos G, Bixler EO, et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes:potential clinical implications. Clin Endocrinol(Oxf),1999.51:205-215.
15. Tochikubo O, Ikeda A, Miyajima E, et al. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension,1996,27: 1318-1324.
16. Ayas NT, White DP, A1-Delaimy WK, et al. A prospective study of self reported sleep duration and incident diabetes in women. Diabetes Care,2003.26:380-384.
17. Palma BD, Gabriel A JR., Bignotto M, et al. Paradoxical sleep deprivation increases plasma endothelin levels. Braz J Med Biol Res,2002,35:75-79.
18.曹雪亮,苗丹民,皇甫恩,等.高原与平原条件下48h完全睡眠剥夺对血压和心率的影响.解放军预防医学杂志,2003,21：334-336.
19. Perry JC, D'Almeida V, Souza FG, et al. Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats. Respir Physiol Neurobiol,2007,156:250-258.
20. Andersen ML, Martins PJ, D'Almeida V, et al. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp Gerontol,2004,39:817-824.
21. VanHelder T, Symons JD, Radomski MW. Effects of sleep deprivation and exercise on glucose tolerance. Aviat Space Environ Med,1993,64(6):487-492.
22. VanHelder T, Radomski MW. Sleep deprivation and the effect on exercise performance. Sports Med,1989,7(4):235-247.
23. Yeh ET, Willerson JT. Coming of age of C-reactive protein:using inflammation markers in cardiology. Circulation,2003,107(3):370-371.
24. Epstein SE, Zhu J, Najafi AH, et al. Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture. Circulation,2009,119(24):3133-3141.
25. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol,2004, 43(4):678-683.
26.段小莉,王百忍,杨唐斌等.抗CRF单克隆抗体和多克隆抗体的制备及其在睡眠剥夺模型大鼠脑内的变化.细胞与分子免疫学杂志,2005,21：476.
27.江波,赵忠新.睡眠剥夺诱发氧化应激反应研究进展.第一军医大学学报,2007,28(2)：201-203.
28. Ramanat han L, Gulyani S, Nienhuis R, et al. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport,2002, 13:1387-1390.
29. Yunoki M, Kawauchi M, Ukita N, et al. Effects of lecit hinized SOD on sequential change in SOD activity after cerebral contusion in rats. Acta Neurochir Suppl,1998, 71:142-145.
30. De Oliveira AC, D'Almeida V, Hipolide DC, et al. Sleep deprivation reduces total plasma homocysteine levels in rats. Can J Physiol Pharmacol,2002,80(3):193-197.
31. Videla LA, Smok G, Troncoso P, et al. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat. Biochem Pharmacol,1995,50(10): 1557-1565.
32.唐庆娟,陶凯忠,胡森森,等.72小时睡眠剥夺大鼠的氧化应激.中国行为医学科学,2003.12(5)：500.
33. Naidoo N, Giang W,Galante RJ,et al. Sleep deprivation induces the unfolded protein response in muse cerebral cortex. J Neurochem,2005,92 (5):1150-1157.
34.Tononi G, Cirelli C. Modulation of brain gene expression during sleep and wakefulness:a review of recent findings. Neuropsychopharmacology,2001,25: S28-S35.
35.Shaw PJ, Cirelli C, Greenspan RJ et al. Correlates of sleep and waking in Drosophila melanogaster. Science,2000,287:1834-1834.
36.Terao A, Steininger TL, Hyder K, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience,2003,116:187-200.
37. Xu C, Bailly-Maitre B. et al. Endoplasmic reticulum stress:cell life and death decisions. J Clin Invest,2005,115:2656-2664.
38. Thomas RD, Kaufman RJ. A trip to the ER:coping with stress. Trends Cell Biol, 2004,14:20-28.
39. kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest,2002,110:1389-139.
40. Luke Wi seman R, Ralch WE. A new pharmacology-drugging stressed folding pathways. TRENDS in Molecular Medicine,2005,8:347-350.
41. Jung HY, Wek RC. Phosphorylation of the a-Subunit of the Eukaryotic Initiation Factor-2 Reduces Protein Synthesis and Enhances Apoptosis in Response to Proteasome inhibition. The Journal of biological chemistry,2005,14:14189-14202.
42. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling:the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol,2006,38:317.
43.赵忠新,主编.临床睡眠障碍学第一版.上海：第二军医大学出版社,2003：30-710.
44. Simpson N, Dinges DF. Sleep and inflammation. Nutrition Reviews,2007,65(3): 244-252.
45. Hublin C. Parinen M, Koskenvuo M, et al. Sleep and mortality:a population-based 22-year follow-up study. Sleep,2007,30(12):1245-1253.
46. Van Dort CJ. Baghdoyan HA. Lydic R. Adenosine A(1) and A(2A)receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci,2009,29(3):871-881.
47. Altena E, Ramautar JR, Van Der Werf YD, et al. Do sleep complaints contribute to age-related cognitive decline? Prog Brain Res,2010,185:181-205.
48.张亚晶,卢才义,黄亚.睡眠剥夺对大鼠心脏的影响及其致心律失常机制研究.血管康复医学杂志,2009,18(3)：224-226.
1. Szmitko PE, Wang CH, Weisel RD, et al. New markers of inflammation and endothelial cell activation:Part Ⅰ. Circulation.2003,108:1917-1923.
2. O'Leary DH, Polak JF, Wolfson SK Jr. Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Reasearch Group. Stroke,1997,28:348-355.
3.于世勇,黄岚,宋耀明,等.心绞痛患者冠状动脉内皮损伤及意义.中华内科杂志,2003,42：473-475.
4. Hirsch AT. Vascular disease, hypertension, and prevention:"from endothelium to clinical events". J Am Coll Cardiol,2003,42:377-379.
5. Shimokawa H. Primary endothelial dysfunction:atherosclerosis. J Mol Cell Cardiol,1999,31:23-37.
6. Duvall WL. Endothelial Dysfunction and Antioxidants. Mt Sinai J Med,2005,72: 71-80.
7. Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res,2003,93:e17-24.
8. Hamed S, Roguin A. Endothelial progenictor cells and atherosclerosis. Harefuah, 2006,145 (5):358-361,397.
9. Boos CJ, Goon Pk, Lip Gy. Endothelial progentor cells in the vascular pathophysiology of hypertension:arterial stiffness, ageing and more. J Hum Hypertension,2006,20(7):475-477.
10. Lau KK, Chan YH, Yiu KH, et al. Burden of carotid atherosclerosis in patients with stroke:relationships with circulating endothelial progenitor cells and hypertension. J Hum Hyperten,2007,1-7.
11.陈剑飞,黄岚,晋军,等.年龄对骨髓内皮祖细胞功能的影响及意义.四川医学,2006,7(5)：231-233.
12.Suzuki T, Nishida M, Futami S, et al. Neoendothelialization after peripheral blood stem cell transplantation in humans:a case report of a Tokaimura nuclear accident victim. Cardiovasc Res,2003,58:487-492.
13. Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30:967-972.
14. Libby P, Ridker PM. Novel inflammatory markers of coronary risk:theory versus practice. Circulation,1999,100:1148-1150.
15. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999,340: 115-126.
16. Libby P. Molecular bases of the acute coronary syndromes. Circulation,1995,91: 2844-2850.
17. Nikkari ST, O'Brien KD, Ferguson M, et al. Interstitial collagenase in human carotid atherosclerosis. Circulation,1995,92:402-406.
18. Lagrand WK, Niessen HWM, Wolbink GJ, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation,1997, 95:97-103.
19. Cemak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood,1993,82:513-520.
20. Biasucci LM,Liuzzo G, Caligiuri G, et al. Episodic activation of the coagulation system in unstalble angina doses not clicit an acute phase reaction. Am J Cardiol, 1996,77(1):85-87.
21. Torzewski J, Torzewski M, Bowyer DE, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic leisions of human coronary areries. Arterioscler Thromb Vase Biol, 1998,18:1386 1392.
22. Ridker PM. High-sensitivity C-reactive protein:potential adjunct for global risk assessmeatin the primary prevention of cardiovascular disease. Circulation,2001, 103(16):1813-1818.
23. Rifai N, Ridker PM. High sensitivity C-reactive protein:A novel and promising marker of coronary heart disease. Clin Chem,2001,47(3):403-411.
24. Tezono K, Sarker KP, Kikuchi H, et al.Bioactivity of the vascular endothelial growth factor trapped in fibrin clots:Production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis,2001,31(2):71-79.
25. Mullenix PS, Andersen CA, Stames BW. Atherosclerosis as inflammation. Ann Vasc Surg,2005,19:130-138.
26. Kanters E, Gijbels MJ, Vergouwe MN, et al. Hematopoietic NF-κB deficiency results in small atherosclerotic lesions with an inflanmlatory phenotype. Blood,2004, 103(3):934-940.
27. Bolick DT, Sfinivasan S, Whetzel A, et al. Lipoxygenase Mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of NF-κB. Arterioscler Thromb Vasc Biol,2006,16(4):16.
28. Rook MF, Neuby AC, Southgate KM. Expression of intercellular adhesion molecules in human saphenous veins:effects of inflammatory cytokines andneointima formation in culture. Atherosclerosis,2000,150(4):33-41.
29. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell,1986,46(5):705-716.
30. Brand K, Page S, Rogler G, et al. Activated transcription factor-kappa B is present in the atherosclerosis lesion. J Clin Invest,1996,97(7):1715-1722.
31. Rodriguez-Porel M, Leman LO, Holmes DR,et al.Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial
32. Sun Juan, Huang YQ. Role of nuclear kappa B signal pathways in process of atherosclerosis. Modem Journal of Integrated Traditional Chinese and Western Medicine,2007,16(15):2158-2162.
33. Ping D, Boekhoudt GH, Rogers EM, et al. Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte Chemoattractant-1 gene. Immunol,1999,162(2):727-734.
34. Menno PJ, De Winther, Edwin Kanters, Georg Kral, et al. Nuclear factor-KB Signaling in Atherogenesis. Arterioscler Thromb Vasc Biol,2005,25:904-914.
35. Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of ciselement "de-coy" against nuclear factor-kB binding site prevents myocardial infaction. NatMed,1997,3(8):894-899.
36. Shin MH, Moon YJ, Seo JE, et al. Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrial electron transport system mediate heat shock2induced MMP-1 and MMP-9 expression. Free Radic Biol Med,2008,44(4): 635-645.
37. Azumi H, Inoue N, Ohashi Y, et al. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris:Important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol,2002,22:1838-1844.
38. Channon KM. Oxidative stress and coronary plaque stability. Arterioscler Thromb Vasc Biol,2002,22:1751-1752.
39. Steinberg D. Low density lipoprotein oxidation its pathobiological significance. J Biol Chem,1997,272(34):20963-20966.
40. Cominacini L, Ulisse G, Pasini AF, et al. Antioxidants inhibit the expression of intercellular cell adhension molecula-1 and vascular cell adhension molecule-1 induced by oxidized LDL on human umbilical endothelial cells. Free Radic Biol Med, 1997,22(1-2):117-127.
41. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res.1999; 85(8):753-766.
42. Lawrence de Koning AB, Werstuck GH, Zhou J, et al. Hyper homocysteinemia and its role in the evelopment of artherosclerosis. Clin Biochen,2003,36(6):431.
43. Galis ZS, Muszynski M, Sukhova GK, et al. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci,1995,748:501-507.
44. Lewis EJ, Bishop J, Bottomley KM, et al. Ro32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitroand in vivo. Br J Pharmacol,1997,121(3):540-546.
45. Orbe J, Fernandez 1, Rodriguez JA. Different expression of MMPs/TIMP-1 in human atherosclerotic lession. Relation to plaque features and vascular bed. Atherosclerosis,2003,170(2):269-276.
46. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis:the good, the bad, and the ugly. Circ Res,2002,90(3):251-262.
47. Kulach A, Dabek J, Glogowska-Ligus J, et al. Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes. Pharmacol Rep,2010,62(6):1108-1116.
48. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
49. Robertson L, Grip L, Mattsson Hulten L, et al. Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention. J Intern Med,2007,262(6):659-667.
50. Shu J, Ren N, Du JB, et al. Increased levels of interleukin-6 and matrix metalloproteinase-9 are of cardiac origin in acute coronary syndrome. Scand Cardiovasc J,2007,41(3):149-154.
51. Silence J, Lupu F, Collen D, et al. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol,2001,21(9):1440-1445
52. Blankenberg S, Rupp recht HJ, Poirier O, et al. Atherogenesis investigators 1 plasma concentrations and genetic variation of matrixmetalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation,2003,107:1579-1585.
53.赵慧颖,徐宝华,马小欣.血清基质金属蛋白酶活性与动脉粥样硬化斑块稳定性的实验观察.中国微循环,2007,23(9)：1700-1702.
54. De Nooijer R, Verklej CJ, Von der Thusen J H, et al. Lesional over expression of matrixmetalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis. Arterioscler Thromb Vase Bio,2006,26(2): 340-346.
55. Ambrose JA, Martinez EE. A new paradigm for plaque stabilization. Circulation, 2002,105(16):2000-2004.
56. Zhao LQ, Si SY. Advances in research matrix metalloproteinases inhibitiors. Chinese Journal New drugs,2004,13(6):494-497.
57. Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymology:dectection of matrix metalloproteinase activity in vascular tissue. Methodol Commun,1995,9(9):974-980
58. Liu G, Wang B, Zhang J, et al. Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice:Role of downregulation of CD40 and MMP-9 expression. J Ethnopharmacol,2009,126(2):350-354.
59. Kim JY, Kim WJ, Kim H, et al. The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappa B in Macrophages:Implication for Atherosclerosis. Immune Netw,2009,9(3):90-97.
60. Rauch I, Iglseder B, Paulweber B, et al. MMP-9 haplotypes and carotid artery atherosclerosis:an association study introducing a novel multicolour multiplex RealTime PCR protocol. Eur J Clin Invest,2008,38(1):24-33.
61. Bellosta S, Baetta R, Canavesi M, et al. Raloxifene inhibits matrix metalloproteinases expression and activity in macrophages and smooth muscle cells. Pharmacol Res,2007,56(2):160-167.
62. Rajagopalan S, Meng XP, Ramasamy S, et al. Reactive oxygen species p reduced bymacrophage-derived foam cells regulate the activity of vascularmatrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest,1996,98:2572-2579.
63. Braunwald E. Shattuck Lecture-Cardiovascular medicine at the turn of the millennium:triumphs concerns and opportunities. N Engl J Med,1997,337: 1360-1369.
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