桃仁改善不同病因所致血液循环障碍的药效及相关分子机制研究
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摘要
血液循环障碍(blood circulation disorder, BCD)是各种原因导致的局部或全身血液循环不足,造成组织器官缺血缺氧等损伤,以及机能、代谢的障碍或衰竭,甚至威胁生命的一种病理生理状态。微循环障碍(microcirculation disturbance, MCD)则主要指局部微血流与微血管水平发生的功能或器质性紊乱,从而造成局部血液灌注的障碍。血液循环障碍相关疾病一直是临床治疗中较为棘手的问题。
中医寒凝血瘀证(cold stagnation and blood stasis syndrome)简称寒证(HS),瘀热互结证(heat stagnation and blood stasis syndrome)简称热证(RS)。研究发现,寒证和热证与一些BCD相关疾病关系密切。中药在治疗寒证和热证中医表征的同时,还有明显改善其BCD的效果。因此,寻找安全、有效的中药防治BCD相关疾病,研究中药的相关药效特性、作用机制具有重要意义。
中药桃仁(Taoren)为蔷薇科植物桃的种仁,已被证明有扩张血管、增加器官血流量、抑制血小板聚集、抗凝血、抗血栓、促纤溶等作用。本课题组前期研究表明,桃仁等中药能治疗不同病理环境下(寒证和热证)的中医表征,其药效可能与不同致病因素所致的BCD不同有关,但尚未对其具体不同特点深入研究。目前也尚未见对不同致病因素所致BCD的中药研究报道。因此,为了进一步认识寒证和热证大鼠模型全身及局部BCD的特点,认识桃仁对两证BCD的药效特性、作用机理及不同特点,我们对两证模型及桃仁干预的影响进行了深入研究及对比分析。研究分三部分：
第一部分：寒凝血瘀证和瘀热互结证模型血液循环障碍的特点研究
目的：研究寒证和热证大鼠模型全身及局部血液循环障碍的不同特点。
方法：将实验大鼠随机分为4组,每组10只：寒证正常组、寒证模型组、热证正常组,热证模型组。以-18±2℃冰柜冷冻,2小时×2次／天,连续7天建立寒证大鼠模型；腹腔注射角叉菜胶溶液连续6天,第7天皮下注射活性干酵母溶液,建立热证大鼠模型。造模第8天对各组动物观察指标：(1)观察动物中医表征,确立造模成功；(2)用微循环检测仪观察耳廓微循环血流速(Fve)、血流态(Fsc)变化；(3)用血流变检测仪检测腹主动脉血粘度(Vis)、血纤维蛋白原含量(Fib)；(4)用组织病理学(HE、PASM、改良PTAH)及病理图像分析法,观察及测量心、肺、肝、肾、脾微小动脉管径(Adia、s-Adia)、微小静脉管径(Vdia、s-Vdia)、肾血管球充盈面积(Gare)、血栓形成率(Trat)、器官实质损伤严重程度评分(Isco)。
结果：(1)两证模型均出现了相应中医表征；(2)血流速两证均明显降低,血流态评分仅有热证明显降低；(3)全血粘度两证均明显增加,纤维蛋白原含量仅有热证明显增加；(4)小动脉管径仅有寒证明显增大,肾血管球充盈面积两证均明显增高；微动脉、微静脉、小静脉管径两证均无明显变化；血栓形成率两证均明显增高；实质细胞损伤评分除热证无明显肺损伤外,两证器官损伤评分均明显增高。
结论：间歇低温冷冻法和角叉菜胶复合注射法可成功建立寒凝血瘀证和瘀热互结证模型。寒证和热证均存在血液循环障碍,其全身表现为血流速降低、血粘度增加；局部表现为微小血管径变化、血栓形成增加、器官实质细胞损伤。寒证与热证血液循环障碍的不同之处：血流态评分(寒证无明显变化,热证明显降低)、纤维蛋白原含量(寒证无明显变化,热证明显增高)、小动脉管径(寒证明显扩张,热证无明显变化)和器官损伤的范围(寒证有明显肺损伤,热证无明显肺损伤)等方面。
第二部分：桃仁对寒凝血瘀证和瘀热互结证血液循环障碍的药效研究
目的：研究桃仁对寒证和热证大鼠血液循环障碍的药效特点。
方法：将实验大鼠分为两批,第一批随机分为4组,每组10只：寒证正常组、寒证模型组、寒证桃仁治疗组、寒证川芎对照组；第二批大鼠随机分为4组,每组10只：热证正常组、热证模型组、热证桃仁治疗组、热证丹参对照组。第一批大鼠按照第一部分方法建立寒证模型；同时寒证桃仁治疗组、寒证川芎对照组每天灌胃给予相应药液,连续7天。第二批大鼠按照第一部分方法建立热证模型；同时热证桃仁治疗组、热证丹参对照组每天灌胃给予相应药液,连续7天。第8天各组动物观察指标：(1)微循环检测仪观察耳廓血流速(Fve)、血流态(Fsc)变化；(2)血流变仪检测血粘度(Vis)、血纤维蛋白原含量(Fib)变化；(3)组织病理学及病理图像分析法,观察各器官小动脉管径(Adia)、肾血管球充盈面积(Gare)、血栓形成率(Trat)、器官实质损伤严重程度评分(Isco)等指标的变化。
结果：桃仁治疗后,两证治疗组血液循环(1)血流速两证均明显增快,血流态评分两证均无明显变化；(2)血粘度两证均有明显降低,纤维蛋白原含量两证均无明显变化；(3)小动脉管径寒证明显减小,热证明显增大；肾血管球充盈面积寒证无明显变化,热证明显减小：血栓形成率两证均无明显变化；器官实质损伤评分除脾脏两证均无明显变化外,肾损伤评分两证均明显降低,心、肺、肝损伤评分寒证均明显降低,热证均无明显变化。
结论：桃仁对寒凝血瘀证和瘀热互结证的血液循环障碍有改善作用,表现为使两证全身血流速加快、血粘度降低,使局部血管舒缩状态改变、使肾的损伤降低。桃仁改善两证循环障碍作用的不同之处是,使寒证小动脉收缩,使热证小动脉扩张；保护寒证心、肺、肝实质细胞,而对热证心、肺、肝实质无明显保护作用。
第三部分：桃仁改善寒凝血瘀证和瘀热互结证血液循环障碍的相关分子机制研究
目的：研究寒证和热证的分子表达特点及不同之处、桃仁干预后两证相关分子表达的变化及不同之处,探讨其可能的机制。
方法：利用第二部分大鼠器官标本(心、肺、肝、肾、脾),共8组(分组同第二部分),进行相关分子病理学检测(免疫组化、TUNEL细胞凋亡、原位杂交)。检测的分子包括：(1)血小板／内皮细胞粘附分子CD31、血管内皮生长因子VEGF; (2)血管内皮细胞凋亡、凋亡抑制蛋白Bcl-2、凋亡诱导蛋白P53；(3)核因子NFκB p65及mRNA、抑制物IκB-a及mRNA;(4)肝CD68阳性巨噬细胞及其蛋白Caspase-1 p20; (5)血管周细胞a-SM-actin、血管平滑肌细胞AT1、ADRB2表达情况。
结果：两模型的分子表达：(1)血管内皮细胞：CD31表达寒证无明显变化,热证明显增高；VEGF表达两证均无明显变化；细胞凋亡两证均明显增多；Bcl-2表达寒证不变而热证减弱；P53(突变型)表达寒证减弱而热证不变；NFκB蛋白表达寒证减弱且无核内活性,但其mRNA表达增强,而热证有核活性增强,但其mRNA表达不变；IKB蛋白表达寒证不变且无核活性,但其mRNA表达增强,而热证有核活性,但其mRNA表达不变；(2)肝巨噬细胞数量寒证明显减少,热证不变；Caspase-1 p20表达两证均无明显变化；(3)血管壁a-SM-actin、AT1表达均不变,ADRB2表达两证均减弱。
桃仁干预后分子表达的变化：(1)血管内皮细胞：CD31表达寒证明显增强,热证不变；VEGF表达寒证不变,热证明显减弱；细胞凋亡两证均不变；Bcl-2表达寒证不变,热证明显增强；P53(突变型)表达两证均无明显变化；NFκB蛋白寒证出现明显核内活性,但其蛋白及mRNA表达不变,而热证核活性不变,其蛋白及mRNA表达均增强；IKB蛋白表达寒证减弱且无核活性,其mRNA表达不变,而热证其核活性减弱,但其蛋白及mRNA表达均不变；(2)肝巨噬细胞数量寒证明显增多,而热证不变；Caspase-1 p20表达强度两证均无明显变化；(3)血管壁a-SM-actin、ADRB2表达均无明显变化,AT1表达寒证明显增强,热证表达不变。
结论：(1)与寒证血液循环障碍关系密切的分子有P53(突变型)、NFκB、IκB、ADRB2,且P53诱导的内皮细胞凋亡增多、巨噬细胞活性降低导致的修复能力下降可促进寒证发生发展；而反复的低温-复温条件所致的血管内皮、平滑肌严重损伤,可能是其NFκB、ADRB2功能降低的原因之一。
(2)与热证血液循环障碍关系密切的分子有CD31、Bcl-2、NFκB、IκB、ADRB2,且CD31介导的血管内皮粘附性增高、Bcl-2抑制所致的内皮细胞凋亡增多、NFκB活性增强所致的各种炎症因子产生和释放,可能是热证发生发展的重要因素。
(3)寒证中受桃仁影响的分子有：CD31、NFκB、IκB、AT1,其中CD31、NFκB活性增强可能不利于血液循环障碍的恢复,而AT1介导的血管强烈的收缩反应、巨噬细胞活性增强,可能是桃仁改善寒证血管麻痹、促进血流及损伤修复的重要因素。
(4)热证中受桃仁影响的分子有：VEGF、Bcl-2、NFκB、IκB,其中VEGF减弱、Bcl-2增强可能是其维持细胞凋亡不变的重要原因；NFκB活性不变但转录增强,则可能与IκB活性降低关系密切,且可能不利于血液循环障碍的恢复。桃仁改善热证血液循环的因素尚待深入研究。
The blood circulation disorder (BCD) is a pathophysiological state induced by local or systemic circulatory inadequacy. It can also result in tissue ischemia hypoxia injury, metabolic disorder, organ failure, even life-threatening. Microcirculation disturbance (MCD), which occurs in the local micro-vascular blood circulation, is an important component of BCD. BCD-related disease has been the thorny problem of therapy.
Cold stagnation and blood stasis syndrome and heat stagnation and blood stasis syndrome (HS and RS), has been found with characteristics of BCD. Traditional Chinese medicine has achieved ideal effects on these two syndromes. So looking for a safe and effective traditional Chinese medicine to prevent BCD-related disease has great significance, as well as studying on its efficacy characteristics and mechanisms.
Taoren, one kind of traditional Chinese medicine, is the seed of heart. It has been found with effects of blood vessel dilation, increasing organ blood flow, inhibiting platelet aggregation, anticoagulation, anti-thrombosis, and so on. Our previous studies found that Taoren act effectively on improving the two syndromes. Therefore, these study committed to find the effects, mechanisms and the differences of Taoren on BCD induced by the two syndromes in rats. The study was divided into three parts:
Part I:Study on the Characteristics of Blood Circulation Disorder in HS and RS Rats
Objective:To study the different characteristics of BCD in HS and RS rats.
Methods:The rats were randomly divided into 4 groups,10 rats in each group:normal control group of HS (HN), model group of HS (HM), normal control group of RS (RN), model group of RS (RM). HM group rats were put into the -18±2℃freezer for 2 hours, two times a day for seven consecutive days. To RM rats, Carrageenan solution was given intraperitoneally for six consecutive days, after that dry yeast solution was given to them subcutaneous ly on the seventh day. On the eighth day, all of the rats were detected the following indexes:(1) the Chinese medicine symptoms, (2) blood flow velocity (Fve) and blood flow score (Fsc), (3) blood viscosity (Vis) and blood fibrinogen (Fib), (4) arteriole and small artery diameter (Adia, s-Adia), venular and small vein diameter (Vdia, s-Vdia), glomerulus area (Gare), thrombosis rate (Trat), organ injury severity score (Isco) (including heart, lung, liver, kidney, spleen) by histopathology analysis (HE, PASM and PTAH staining).
Results:(1) The corresponding Chinese medicine symptoms appeared respectively in both HM and RM rats. (2) The decreased blood flow velocity appeared in both HM and RM rats, while the decreased blood flow score appeared just in RM rats. (3) The increased blood viscosity appeared in both HM and RM rats, while the increased blood fibrinogen appeared just in RM rats. (4) The increased small artery diameter appeared just in HM rats. The increased glomerulus area appeared in both HM and RM rats. The arteriole, venular and small vein diameter did not change significantly in both HM and RM rats. The increased thrombosis rate and increased organ injury severity score appeared respectively in both HM and RM rats, in addition to the lung injury severity score in RM rats.
Conclusion:There was BCD in rats with cold stagnation and blood stasis syndrome and heat stagnation and blood stasis syndrome, induced by frozen method and Carrageenan respectively. Its systemic manifestations included decreased blood flow velocity and increased blood viscosity. Its local manifestations included changes of vascular diameter, thrombosis, organ injury. The differences between HS and RS included blood flow score, blood fibrinogen, small artery diameter and the range of organ injury.
Part II:Effects of Taoren on Blood Circulation Disorder in HS and RS Rats
Objective:To study the different effects of Taoren on BCD in HS and RS rats.
Methods:The rats were randomly divided into 2 part,4 groups in one part, 10 rats in each group, the 1st 4 groups:normal control group of HS (HN), model group of HS (HM), Taoren treatment group of HS(HT), Chuanxiong control group of HS(HC), the 2nd 4 groups:normal control group of RS(RN), model group of RS (RM), Taoren treatment group of RS(RT), Danshen control group of RS(RD). HM, HT and HC rats were put into the -18±2℃freezer as Part I. The carrageenan and dry yeast solution were given to RM, RT and RD rats as PartⅠ. At the same time, the corresponding traditional Chinese medicines were given to HT, HC, RT and RD rats for sever consecutive days. On the eighth day, all of the rats were detected the following indexes:(1) blood flow velocity (Fve) and blood flow score (Fsc), (2) blood viscosity (Vis) and blood fibrinogen (Fib), (3) small artery diameter (s-Adia), glomerulus area (Gare), thrombosis rate (Trat), organ injury severity score (Isco) (including heart, lung, liver, kidney, spleen) by histopathology analysis (HE, PASM and PTAH staining).
Results:The effects of Taoren on BCD included:(1) The increased blood flow velocity appeared in both HT and RT rats, while the blood flow score did not change in both HT and RT rats. (2) The decreased blood viscosity appeared in both HT and RT rats, while the blood fibrinogen did not change in both HT and RT rats. (3) The decreased small artery diameter appeared just in HT rats, while the increased small artery diameter appeared in RT rats. The decreased glomerulus area appeared in RT rats, while the glomerulus area did not change in HT rats. The thrombosis rate did not change in both HT and RT rats. The decreased kidney injury severity score appeared in both HT and RT rats, while the decreased injury severity score of heart, lung and liver appeared just in HT rats. The spleen injury severity score did not change in both HT and RT rats.
Conclusion:Taoren improved BCD in rats with HS and RS. The improvements lied in increasing blood flow velocity, decreasing blood viscosity, regulating the local vascular diameter and protecting kidney from injury. The different effects of Taoren on the two syndromes included:decreasing small artery diameter and protecting more organs from injury in HS rats, but increasing small artery diameter and protecting only for kidney from injury in RS rats.
PartⅢ:Molecular Mechanisms of Taoren on Blood Circulation Disorder in HS and RS Rats
Objective:To study the different molecular expression of HS and RS, the molecular mechanisms of Taoren on BCD in the two syndromes.
Methods:The organ specimens were derived from PartⅡ. All of the specimens were detected the molecular expression by histopathology analysis (IHC, TUNEL, ISH). The indexes included:(1) adhesion molecule CD31 and vascular endothelial cell (VEC) growth factor VEGF, (2) VEC apoptosis, apoptotic inhibitor Bcl-2, apoptotic induced protein P53, (3) nucleus factor NFκB p65 and mRNA, inhibitor IκB-a and mRNA, (4) hepatic CD68+ macrophage and Caspase-1 P20 protein, (5) vascular pericyte (VPC) protein a-SM-actin, vascular smooth muscle cell (VSMC) receptor AT1 and ADRB2.
Results:Molecular expression in HM and RM rats:(1) Increased CD31 expression appeared just in RM rats, while it did not change in HM rats. VEGF expression did not change in both HM and RM rats. Increased apoptosis appeared in both HM and RM rats. Decreased Bcl-2 expression appeared just in RM rats, while it did not change in HM rats. Decreased P53 expression appeared just in HM rats, while it did not change in RM rats. It was decreased NFκB protein, increased its mRNA and without its nucleus expression in HM rats. While in RM rats, it was decreased NFκB protein, increased its nucleus expression and without its mRNA change. It was increased IκB mRNA, without change on its protein and its nucleus expression in HM rats. While in RM rats, it was increased nucleus expression, without change on its protein and its mRNA. (2) Decreased hepatic CD68+ macrophage appeared just in HM rats, while it did not change in RM rats. Caspase-1 P20 protein did not change in both HM and RM rats. (3) Decreased ADRB2 expression appeared in both HM and RM rats, while expression of a-SM-actin and AT1 did not change in the two models.
The changes of molecular expression in HT and RT:(1) Increased CD31 expression appeared just in HT rats, while it did not change in RT rats. Decreased VEGF expression appeared just in RT rats, while it did not change in HT rats. Apoptosis did not change in both HT and RT rats. Increased Bcl-2 expression appeared just in RT rats, while it did not change in HT rats. P53 expression did not change in both HT and RT rats. It was increased NFκB nucleus expression, without change on its protein and its mRNA in HT rats. While in RT rats, it was increased NFκB protein and its mRNA, without change on its nucleus expression. It was decreased IκB protein, without its nucleus expression and its mRNA change in HT rats. While in RT rats, it was decreased nucleus expression, without change on its protein and its mRNA.
Conclusion:(1) Molecules closely related to HS included P53, NFκB, IκB and ADRB2. The promoting factors of HS might be the increased P53-induced apoptosis of endothelial cells and the decreased repair capacity of macrophages. The serious injury of endothelial cells and smooth muscle cells, caused by repeated freezing and rewarming, might be the reason of decreased activity of NFκB and ADRB2.
(2) Molecules closely related to RS included CD31, Bcl-2, NFκB, IκB and ADRB2. The promoting factors of RS might be the increased CD31-induced adhesion and Bcl-2-related apoptosis of endothelial cells, besides of the increased inflammatory factor induced by activated NFκB.
(3) Molecules affected by Taoren in HS included CD31, NFκB, IκB and AT1. The inhibited factors of circulation recovery might be increased CD31 and activated NFκB. The acceleration of circulation recovery might be the vascular contractile response induced by AT1 and the increased repair capacity of macrophages.
(4) Molecules affected by Taoren in RS included VEGF, Bcl-2, NFκB and IκB. The persistent factors of apoptosis might be the decreased VEGF and increased Bcl-2 of endothelial cells. The persistent activity and increased transcription of NFκB might be closely related to the decreased activity of IκB. These might not be conductive to the recovery of BCD, and remained to be in-depth study.
中医寒凝血瘀证(cold stagnation and blood stasis syndrome)简称寒证(HS),瘀热互结证(heat stagnation and blood stasis syndrome)简称热证(RS)。研究发现,寒证和热证与一些BCD相关疾病关系密切。中药在治疗寒证和热证中医表征的同时,还有明显改善其BCD的效果。因此,寻找安全、有效的中药防治BCD相关疾病,研究中药的相关药效特性、作用机制具有重要意义。
中药桃仁(Taoren)为蔷薇科植物桃的种仁,已被证明有扩张血管、增加器官血流量、抑制血小板聚集、抗凝血、抗血栓、促纤溶等作用。本课题组前期研究表明,桃仁等中药能治疗不同病理环境下(寒证和热证)的中医表征,其药效可能与不同致病因素所致的BCD不同有关,但尚未对其具体不同特点深入研究。目前也尚未见对不同致病因素所致BCD的中药研究报道。因此,为了进一步认识寒证和热证大鼠模型全身及局部BCD的特点,认识桃仁对两证BCD的药效特性、作用机理及不同特点,我们对两证模型及桃仁干预的影响进行了深入研究及对比分析。研究分三部分：
第一部分：寒凝血瘀证和瘀热互结证模型血液循环障碍的特点研究
目的：研究寒证和热证大鼠模型全身及局部血液循环障碍的不同特点。
方法：将实验大鼠随机分为4组,每组10只：寒证正常组、寒证模型组、热证正常组,热证模型组。以-18±2℃冰柜冷冻,2小时×2次／天,连续7天建立寒证大鼠模型；腹腔注射角叉菜胶溶液连续6天,第7天皮下注射活性干酵母溶液,建立热证大鼠模型。造模第8天对各组动物观察指标：(1)观察动物中医表征,确立造模成功；(2)用微循环检测仪观察耳廓微循环血流速(Fve)、血流态(Fsc)变化；(3)用血流变检测仪检测腹主动脉血粘度(Vis)、血纤维蛋白原含量(Fib)；(4)用组织病理学(HE、PASM、改良PTAH)及病理图像分析法,观察及测量心、肺、肝、肾、脾微小动脉管径(Adia、s-Adia)、微小静脉管径(Vdia、s-Vdia)、肾血管球充盈面积(Gare)、血栓形成率(Trat)、器官实质损伤严重程度评分(Isco)。
结果：(1)两证模型均出现了相应中医表征；(2)血流速两证均明显降低,血流态评分仅有热证明显降低；(3)全血粘度两证均明显增加,纤维蛋白原含量仅有热证明显增加；(4)小动脉管径仅有寒证明显增大,肾血管球充盈面积两证均明显增高；微动脉、微静脉、小静脉管径两证均无明显变化；血栓形成率两证均明显增高；实质细胞损伤评分除热证无明显肺损伤外,两证器官损伤评分均明显增高。
结论：间歇低温冷冻法和角叉菜胶复合注射法可成功建立寒凝血瘀证和瘀热互结证模型。寒证和热证均存在血液循环障碍,其全身表现为血流速降低、血粘度增加；局部表现为微小血管径变化、血栓形成增加、器官实质细胞损伤。寒证与热证血液循环障碍的不同之处：血流态评分(寒证无明显变化,热证明显降低)、纤维蛋白原含量(寒证无明显变化,热证明显增高)、小动脉管径(寒证明显扩张,热证无明显变化)和器官损伤的范围(寒证有明显肺损伤,热证无明显肺损伤)等方面。
第二部分：桃仁对寒凝血瘀证和瘀热互结证血液循环障碍的药效研究
目的：研究桃仁对寒证和热证大鼠血液循环障碍的药效特点。
方法：将实验大鼠分为两批,第一批随机分为4组,每组10只：寒证正常组、寒证模型组、寒证桃仁治疗组、寒证川芎对照组；第二批大鼠随机分为4组,每组10只：热证正常组、热证模型组、热证桃仁治疗组、热证丹参对照组。第一批大鼠按照第一部分方法建立寒证模型；同时寒证桃仁治疗组、寒证川芎对照组每天灌胃给予相应药液,连续7天。第二批大鼠按照第一部分方法建立热证模型；同时热证桃仁治疗组、热证丹参对照组每天灌胃给予相应药液,连续7天。第8天各组动物观察指标：(1)微循环检测仪观察耳廓血流速(Fve)、血流态(Fsc)变化；(2)血流变仪检测血粘度(Vis)、血纤维蛋白原含量(Fib)变化；(3)组织病理学及病理图像分析法,观察各器官小动脉管径(Adia)、肾血管球充盈面积(Gare)、血栓形成率(Trat)、器官实质损伤严重程度评分(Isco)等指标的变化。
结果：桃仁治疗后,两证治疗组血液循环(1)血流速两证均明显增快,血流态评分两证均无明显变化；(2)血粘度两证均有明显降低,纤维蛋白原含量两证均无明显变化；(3)小动脉管径寒证明显减小,热证明显增大；肾血管球充盈面积寒证无明显变化,热证明显减小：血栓形成率两证均无明显变化；器官实质损伤评分除脾脏两证均无明显变化外,肾损伤评分两证均明显降低,心、肺、肝损伤评分寒证均明显降低,热证均无明显变化。
结论：桃仁对寒凝血瘀证和瘀热互结证的血液循环障碍有改善作用,表现为使两证全身血流速加快、血粘度降低,使局部血管舒缩状态改变、使肾的损伤降低。桃仁改善两证循环障碍作用的不同之处是,使寒证小动脉收缩,使热证小动脉扩张；保护寒证心、肺、肝实质细胞,而对热证心、肺、肝实质无明显保护作用。
第三部分：桃仁改善寒凝血瘀证和瘀热互结证血液循环障碍的相关分子机制研究
目的：研究寒证和热证的分子表达特点及不同之处、桃仁干预后两证相关分子表达的变化及不同之处,探讨其可能的机制。
方法：利用第二部分大鼠器官标本(心、肺、肝、肾、脾),共8组(分组同第二部分),进行相关分子病理学检测(免疫组化、TUNEL细胞凋亡、原位杂交)。检测的分子包括：(1)血小板／内皮细胞粘附分子CD31、血管内皮生长因子VEGF; (2)血管内皮细胞凋亡、凋亡抑制蛋白Bcl-2、凋亡诱导蛋白P53；(3)核因子NFκB p65及mRNA、抑制物IκB-a及mRNA;(4)肝CD68阳性巨噬细胞及其蛋白Caspase-1 p20; (5)血管周细胞a-SM-actin、血管平滑肌细胞AT1、ADRB2表达情况。
结果：两模型的分子表达：(1)血管内皮细胞：CD31表达寒证无明显变化,热证明显增高；VEGF表达两证均无明显变化；细胞凋亡两证均明显增多；Bcl-2表达寒证不变而热证减弱；P53(突变型)表达寒证减弱而热证不变；NFκB蛋白表达寒证减弱且无核内活性,但其mRNA表达增强,而热证有核活性增强,但其mRNA表达不变；IKB蛋白表达寒证不变且无核活性,但其mRNA表达增强,而热证有核活性,但其mRNA表达不变；(2)肝巨噬细胞数量寒证明显减少,热证不变；Caspase-1 p20表达两证均无明显变化；(3)血管壁a-SM-actin、AT1表达均不变,ADRB2表达两证均减弱。
桃仁干预后分子表达的变化：(1)血管内皮细胞：CD31表达寒证明显增强,热证不变；VEGF表达寒证不变,热证明显减弱；细胞凋亡两证均不变；Bcl-2表达寒证不变,热证明显增强；P53(突变型)表达两证均无明显变化；NFκB蛋白寒证出现明显核内活性,但其蛋白及mRNA表达不变,而热证核活性不变,其蛋白及mRNA表达均增强；IKB蛋白表达寒证减弱且无核活性,其mRNA表达不变,而热证其核活性减弱,但其蛋白及mRNA表达均不变；(2)肝巨噬细胞数量寒证明显增多,而热证不变；Caspase-1 p20表达强度两证均无明显变化；(3)血管壁a-SM-actin、ADRB2表达均无明显变化,AT1表达寒证明显增强,热证表达不变。
结论：(1)与寒证血液循环障碍关系密切的分子有P53(突变型)、NFκB、IκB、ADRB2,且P53诱导的内皮细胞凋亡增多、巨噬细胞活性降低导致的修复能力下降可促进寒证发生发展；而反复的低温-复温条件所致的血管内皮、平滑肌严重损伤,可能是其NFκB、ADRB2功能降低的原因之一。
(2)与热证血液循环障碍关系密切的分子有CD31、Bcl-2、NFκB、IκB、ADRB2,且CD31介导的血管内皮粘附性增高、Bcl-2抑制所致的内皮细胞凋亡增多、NFκB活性增强所致的各种炎症因子产生和释放,可能是热证发生发展的重要因素。
(3)寒证中受桃仁影响的分子有：CD31、NFκB、IκB、AT1,其中CD31、NFκB活性增强可能不利于血液循环障碍的恢复,而AT1介导的血管强烈的收缩反应、巨噬细胞活性增强,可能是桃仁改善寒证血管麻痹、促进血流及损伤修复的重要因素。
(4)热证中受桃仁影响的分子有：VEGF、Bcl-2、NFκB、IκB,其中VEGF减弱、Bcl-2增强可能是其维持细胞凋亡不变的重要原因；NFκB活性不变但转录增强,则可能与IκB活性降低关系密切,且可能不利于血液循环障碍的恢复。桃仁改善热证血液循环的因素尚待深入研究。
The blood circulation disorder (BCD) is a pathophysiological state induced by local or systemic circulatory inadequacy. It can also result in tissue ischemia hypoxia injury, metabolic disorder, organ failure, even life-threatening. Microcirculation disturbance (MCD), which occurs in the local micro-vascular blood circulation, is an important component of BCD. BCD-related disease has been the thorny problem of therapy.
Cold stagnation and blood stasis syndrome and heat stagnation and blood stasis syndrome (HS and RS), has been found with characteristics of BCD. Traditional Chinese medicine has achieved ideal effects on these two syndromes. So looking for a safe and effective traditional Chinese medicine to prevent BCD-related disease has great significance, as well as studying on its efficacy characteristics and mechanisms.
Taoren, one kind of traditional Chinese medicine, is the seed of heart. It has been found with effects of blood vessel dilation, increasing organ blood flow, inhibiting platelet aggregation, anticoagulation, anti-thrombosis, and so on. Our previous studies found that Taoren act effectively on improving the two syndromes. Therefore, these study committed to find the effects, mechanisms and the differences of Taoren on BCD induced by the two syndromes in rats. The study was divided into three parts:
Part I:Study on the Characteristics of Blood Circulation Disorder in HS and RS Rats
Objective:To study the different characteristics of BCD in HS and RS rats.
Methods:The rats were randomly divided into 4 groups,10 rats in each group:normal control group of HS (HN), model group of HS (HM), normal control group of RS (RN), model group of RS (RM). HM group rats were put into the -18±2℃freezer for 2 hours, two times a day for seven consecutive days. To RM rats, Carrageenan solution was given intraperitoneally for six consecutive days, after that dry yeast solution was given to them subcutaneous ly on the seventh day. On the eighth day, all of the rats were detected the following indexes:(1) the Chinese medicine symptoms, (2) blood flow velocity (Fve) and blood flow score (Fsc), (3) blood viscosity (Vis) and blood fibrinogen (Fib), (4) arteriole and small artery diameter (Adia, s-Adia), venular and small vein diameter (Vdia, s-Vdia), glomerulus area (Gare), thrombosis rate (Trat), organ injury severity score (Isco) (including heart, lung, liver, kidney, spleen) by histopathology analysis (HE, PASM and PTAH staining).
Results:(1) The corresponding Chinese medicine symptoms appeared respectively in both HM and RM rats. (2) The decreased blood flow velocity appeared in both HM and RM rats, while the decreased blood flow score appeared just in RM rats. (3) The increased blood viscosity appeared in both HM and RM rats, while the increased blood fibrinogen appeared just in RM rats. (4) The increased small artery diameter appeared just in HM rats. The increased glomerulus area appeared in both HM and RM rats. The arteriole, venular and small vein diameter did not change significantly in both HM and RM rats. The increased thrombosis rate and increased organ injury severity score appeared respectively in both HM and RM rats, in addition to the lung injury severity score in RM rats.
Conclusion:There was BCD in rats with cold stagnation and blood stasis syndrome and heat stagnation and blood stasis syndrome, induced by frozen method and Carrageenan respectively. Its systemic manifestations included decreased blood flow velocity and increased blood viscosity. Its local manifestations included changes of vascular diameter, thrombosis, organ injury. The differences between HS and RS included blood flow score, blood fibrinogen, small artery diameter and the range of organ injury.
Part II:Effects of Taoren on Blood Circulation Disorder in HS and RS Rats
Objective:To study the different effects of Taoren on BCD in HS and RS rats.
Methods:The rats were randomly divided into 2 part,4 groups in one part, 10 rats in each group, the 1st 4 groups:normal control group of HS (HN), model group of HS (HM), Taoren treatment group of HS(HT), Chuanxiong control group of HS(HC), the 2nd 4 groups:normal control group of RS(RN), model group of RS (RM), Taoren treatment group of RS(RT), Danshen control group of RS(RD). HM, HT and HC rats were put into the -18±2℃freezer as Part I. The carrageenan and dry yeast solution were given to RM, RT and RD rats as PartⅠ. At the same time, the corresponding traditional Chinese medicines were given to HT, HC, RT and RD rats for sever consecutive days. On the eighth day, all of the rats were detected the following indexes:(1) blood flow velocity (Fve) and blood flow score (Fsc), (2) blood viscosity (Vis) and blood fibrinogen (Fib), (3) small artery diameter (s-Adia), glomerulus area (Gare), thrombosis rate (Trat), organ injury severity score (Isco) (including heart, lung, liver, kidney, spleen) by histopathology analysis (HE, PASM and PTAH staining).
Results:The effects of Taoren on BCD included:(1) The increased blood flow velocity appeared in both HT and RT rats, while the blood flow score did not change in both HT and RT rats. (2) The decreased blood viscosity appeared in both HT and RT rats, while the blood fibrinogen did not change in both HT and RT rats. (3) The decreased small artery diameter appeared just in HT rats, while the increased small artery diameter appeared in RT rats. The decreased glomerulus area appeared in RT rats, while the glomerulus area did not change in HT rats. The thrombosis rate did not change in both HT and RT rats. The decreased kidney injury severity score appeared in both HT and RT rats, while the decreased injury severity score of heart, lung and liver appeared just in HT rats. The spleen injury severity score did not change in both HT and RT rats.
Conclusion:Taoren improved BCD in rats with HS and RS. The improvements lied in increasing blood flow velocity, decreasing blood viscosity, regulating the local vascular diameter and protecting kidney from injury. The different effects of Taoren on the two syndromes included:decreasing small artery diameter and protecting more organs from injury in HS rats, but increasing small artery diameter and protecting only for kidney from injury in RS rats.
PartⅢ:Molecular Mechanisms of Taoren on Blood Circulation Disorder in HS and RS Rats
Objective:To study the different molecular expression of HS and RS, the molecular mechanisms of Taoren on BCD in the two syndromes.
Methods:The organ specimens were derived from PartⅡ. All of the specimens were detected the molecular expression by histopathology analysis (IHC, TUNEL, ISH). The indexes included:(1) adhesion molecule CD31 and vascular endothelial cell (VEC) growth factor VEGF, (2) VEC apoptosis, apoptotic inhibitor Bcl-2, apoptotic induced protein P53, (3) nucleus factor NFκB p65 and mRNA, inhibitor IκB-a and mRNA, (4) hepatic CD68+ macrophage and Caspase-1 P20 protein, (5) vascular pericyte (VPC) protein a-SM-actin, vascular smooth muscle cell (VSMC) receptor AT1 and ADRB2.
Results:Molecular expression in HM and RM rats:(1) Increased CD31 expression appeared just in RM rats, while it did not change in HM rats. VEGF expression did not change in both HM and RM rats. Increased apoptosis appeared in both HM and RM rats. Decreased Bcl-2 expression appeared just in RM rats, while it did not change in HM rats. Decreased P53 expression appeared just in HM rats, while it did not change in RM rats. It was decreased NFκB protein, increased its mRNA and without its nucleus expression in HM rats. While in RM rats, it was decreased NFκB protein, increased its nucleus expression and without its mRNA change. It was increased IκB mRNA, without change on its protein and its nucleus expression in HM rats. While in RM rats, it was increased nucleus expression, without change on its protein and its mRNA. (2) Decreased hepatic CD68+ macrophage appeared just in HM rats, while it did not change in RM rats. Caspase-1 P20 protein did not change in both HM and RM rats. (3) Decreased ADRB2 expression appeared in both HM and RM rats, while expression of a-SM-actin and AT1 did not change in the two models.
The changes of molecular expression in HT and RT:(1) Increased CD31 expression appeared just in HT rats, while it did not change in RT rats. Decreased VEGF expression appeared just in RT rats, while it did not change in HT rats. Apoptosis did not change in both HT and RT rats. Increased Bcl-2 expression appeared just in RT rats, while it did not change in HT rats. P53 expression did not change in both HT and RT rats. It was increased NFκB nucleus expression, without change on its protein and its mRNA in HT rats. While in RT rats, it was increased NFκB protein and its mRNA, without change on its nucleus expression. It was decreased IκB protein, without its nucleus expression and its mRNA change in HT rats. While in RT rats, it was decreased nucleus expression, without change on its protein and its mRNA.
Conclusion:(1) Molecules closely related to HS included P53, NFκB, IκB and ADRB2. The promoting factors of HS might be the increased P53-induced apoptosis of endothelial cells and the decreased repair capacity of macrophages. The serious injury of endothelial cells and smooth muscle cells, caused by repeated freezing and rewarming, might be the reason of decreased activity of NFκB and ADRB2.
(2) Molecules closely related to RS included CD31, Bcl-2, NFκB, IκB and ADRB2. The promoting factors of RS might be the increased CD31-induced adhesion and Bcl-2-related apoptosis of endothelial cells, besides of the increased inflammatory factor induced by activated NFκB.
(3) Molecules affected by Taoren in HS included CD31, NFκB, IκB and AT1. The inhibited factors of circulation recovery might be increased CD31 and activated NFκB. The acceleration of circulation recovery might be the vascular contractile response induced by AT1 and the increased repair capacity of macrophages.
(4) Molecules affected by Taoren in RS included VEGF, Bcl-2, NFκB and IκB. The persistent factors of apoptosis might be the decreased VEGF and increased Bcl-2 of endothelial cells. The persistent activity and increased transcription of NFκB might be closely related to the decreased activity of IκB. These might not be conductive to the recovery of BCD, and remained to be in-depth study.
引文
[1]刘秀华.血液微循环与心血管疾病[J].微循环学杂志,2007,17(3)：1-6.
[2]王宏宇,胡大一.心脏和血管疾病的早期检测：功能性替代指标(上)[J].中国医刊,2006,41(2)：61-62.
[3]张世增,寇勇,郭娟,等.缺血性心脑血管病早期降纤治疗的疗效观察[J].现代预防医学,2003,30(1)：22-23.
[4]谢景荣,陈健,李敬兰,等.白细胞自发活化与粘附分子CDllb在高胆固醇血症中的应用[J].天津医科大学学报,2002,8(2)：149-150.
[5]热匹克,胡月明.心血管疾患合并甲襞微循环障碍性疾病应用蝮蛇抗栓酶治疗106例疗效观察[J].农垦医学,1999,21(1)：47-48.
[6]吴以岭.络病学概要[J].疑难病杂志,2004,3(1)：37-39.
[7]赵步长,庄欣.论心脑血管疾病的脑心同治原则[J].世界中医药,2006,3(1)37-39.
[8]陈奇.中药药理研究方法的发展概况与特点.中国药理学会第十次全国学术会议,中国天津,2009,247-252.
[9]王殿俊,刘小浩,金辉,等.热毒血瘀证动物模型的研究.江苏中医,1992,3：39-40.
[10]杨进,陆平成.家兔“热毒血癖证”系列动物模型的试制.南京中医药大学学报,1995,11(2)：70-72.
[11]邓家刚.一种瘀热互结证动物模型的建立方法[Z].医药评价,中医药理研究技术领域：CN101933951A,2011.01.05.
[12]Daniel De Backer, Gustavo Ospina-Tascon, Diamantino Salgado, ex al. Monitoring the microcirculation in the critically ill patient:current methods and future approaches [J].2010,36 (11):1813-1825.
[13]Trzeciak, S., J. V. McCoy, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med, 2008,34(12):2210-2217.
[14]Boldt, J. and C. Ince. The impact of fluid therapy on microcirculation and tissue oxygenation in hypovolemic patients:a review. Intensive Care Med, 2010,36(8):1299-1308.
[15]Creteur, J., D. De Backer, et al. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care,2006, Med 32(4):516-523.
[16]Boerma, E. C., M. A. Kuiper, et al. Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock:a prospective observational study. Intensive Care Med,2008,34(7):1294-1298.
[17]吴垦莉,张珊珊.寒凝血瘀证动物模型的研制[J].中国中医基础医学杂志,1996,2(2)：49-51.
[18]倪瑾,夏友详,张珊珊.寒凝血瘀与家兔血管关系的实验观察[J].微循环技术杂志,1996,(2)：96-98.
[19]郑小伟.寒凝血瘀证动物模型的量化研究[J].浙江中医学院学报,1999,23(2)：43-45.
[20]杨士友,孙备,裴月梅.风寒表证和寒凝血瘀证动物模型的研究[J].中国中医基础医学杂志,1997,3(1)：54-56.
[21]成秀梅,杜惠兰,李丹.寒凝血瘀证动物模型的创建[J].中国中医基础医学杂志,2005,11(8)：604-605.
[22]谢文光,马晓昌,邵宁生,等.赤芍治疗热毒血瘀证的血清蛋白质组变化的初步研究.中国中西医结合杂志,2005,25(6)：520-524.
[23]陈秋红,周小梅,多杰,等.青鹏胶囊解热镇痛及抗炎作用实验研究[J].山东中医杂志,2006,25(6)：407-409.
[24]魏陵博,彭敏,戎冬梅.通心络胶囊对角叉菜胶所致大鼠血栓形成的影响[J].中西医结合心脑血管病杂志,2006,9,4(9)：785-786.
[25]郭宏伟,邓家刚,郑作文,等.平性药对LPS所致淤热互结证大鼠微循环的影响[J].时珍国医国药,2011,22(4)：838-839.
[26]田牛,李玉珍,刘育英.血瘀证的微循环研究[J].中国中西医结合杂志,2001,21(4)：248-251.
[27]刘育英编著.微循环图谱.北京：人民军医出版社,2005：1-178.
[28]郭淑贞.血瘀证(心肌缺血)动物模型及其相关蛋白质组学研究[D].北京中医药大学：北京中医药大学,2007.
[29]姜智浩,王怡,范祥,等.血瘀证动物模型舌体动脉血管形态研究[J].辽宁中医杂志,2008,35(7)：1098-1099.
[30]张斌,王中华,王江蓉,等.血瘀型肝纤维化大鼠模型的建立与评价[J].中国中医基础医学杂志,2006,12(11)：836-838.
[31]王淑娟,王建中.血液流变学检验及其临床应用[J].中国医刊,2003,38(4)：215～216.
[32]俞纯山.血流变学研究进展及其临床应用[J].实用医学杂志,2002,18(5)：49～450.
[33]胡小勤.高血压病血瘀证血管内皮细胞损伤模型的研究[D].暨南大学：暨南大学,2007.
[34]Hertig, A. and E. Rondeau. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury. J Am Soc Nephrol,2004,15(4):844-853.
[35]席春生,孙雪峰,陈香关,等.调控纤维蛋自水平对不同鼠龄肾脏炎症反应的影响.中华老年医学杂志.2005,24(15)：365.
[36]肇启春.瓜蒌皮注射液对血瘀证模型大鼠血液流变学及血管内皮素的影响[D].大连：大连医科大学,2007.
[37]金末淑.艾灸膈俞穴对寒凝血瘀证模型大鼠血液流变学的实验研究[D].北京：北京中医药大学,2009.
[38]马小娜.病证结合子宫内膜异位症大鼠模型的建立与评价[D].北京中医药大学：北京中医药大学,2011.
[39]李春阳,李林,魏海峰,等.局灶性脑缺血大鼠血瘀证相关指标和脑损伤病理生理的动态变化[J].中国中西医结合急救杂志,2007,(5)：259-263.
[40]王巧云.黄芪注射液对血瘀证兔血液流变学的影响[J].中药药理与临床,2004,(2)：19-20.
[41]杨超,周岩,孙晓红,等.具有中医“热毒血瘀证”表征的大鼠血液成分和流变学变化[J].中国比较医学杂志,2007,(10)：607-612.
[42]田牛.主要器官微循环的特点及其改变[J].微循环技术杂志,1995,(1)：41-50.
[43]田牛,胡金麟.临床微循环观测结果的数学表达[J].中国生物医学工程学报,1996,(1)：14-17.
[44]田牛,姜澜.临床微循环“综合定量评价”理论基础的再认识[J].微循环学杂志,1994,(2)：l-3.
[45]田牛.加快我国临床微循环的发展[J].中国微循环,1998,(1)：50-53.
[46]秦任甲.动脉粥样硬化好发部位血液流态和参数分析[J].中国医学物理学杂志,2009,26(2)：1102-1104.
[47]李静,冯建涛,孙全梅,等.血管功能界面微纳尺度形貌的表征与仿生制备[J].微循环学杂志,2011,(2)：80.
[48]张英骏,钱冠清.显微电视在微循环中的应用[J].医学研究通讯,1982,(6)：27.
[49]金惠铭.应用多功能显微图象测量仪测量微血管管径、流速和数目[J].上海第一医学院学报,1985,(5)：395-396.
[50]胡金麟.基于灰度的微血管管径自跟踪算法[J].中国生物医学工程学报,1998,(2)：78-81、91.
[51]钱冠清.各种止血因子在血栓诊断中的作用[J].国外医学参考资料(内科学分册),1974,(11)：492-494.
[52]张云芳.活血止痛液对小鼠凝血时间及微循环影响的实验研究[J].中医正骨,1999,11(12)：16.
[53]贾振华.血管内皮细胞结构及其功能变化与血瘀证形成关系的研究[D].山东：山东中医药大学,2002.
[54]胡建鹏.益气活血法对脑缺血再灌注大鼠神经细胞凋亡Fas/FasL信号转导通路与调控的研究[D].北京：北京中医药大学,2004.
[55]林兰,王波,魏海峰,等.低能量He-Ne激光对实验性家兔糖尿病脑梗塞皮层脑微循环的影响[J].中国中医药信息杂志,2002,9(2)：24-26.
[56]Gules, I., M. Satoh, et al. Comparison of three rat models of cerebral vasospasm. Am J Physiol Heart Circ Physiol,2002,283(6):H2551-2559.
[57]张俊杰,刘茜,张磊,等.丹参对微循环障碍的调节作用[J].中国微循环,2002,6(5)：316.
[58]滕久祥,彭芝配,郭建生,等.九气拈痛胶囊对大鼠“寒凝血瘀”模型的影响[J].新中医,1998,30(11)：32-33.
[59]张清波,顾克仁,王玉润.用激光多普耳血流量仪及胆汁流量计测定桃仁提取物对肝脏微循环的影响.[J]上海中医药杂志,1985,7：45-46.
[1]王世军,姬广臣,史仁华,等.葛根素、川芎嗪、丹参注射液对大脑中动脉阻断大鼠脑微循环血流量的影响[J].中成药,2000,22(6)：38-40.
[2]Han, J. Y., Y. Horie, et al. Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery. World J Gastroenterol,2007,13(26):3581-3591.
[3]李俊杰,赵自刚,牛春雨,等.夏至草醇提物对急性微循环障碍大鼠一氧化氮及其合酶的影响[J].微循环学杂志,2007,17(3)：27-28、30、80、82-83.
[4]李俊杰,王伟平,赵自刚,等.夏至草醇提物对急性微循环障碍大鼠自由基损伤的影响[J].中国微循环,2007,11(5)：300-302.
[5]杨淼,刘玉玉,李淑娟.黄芪注射液对内毒素诱导大鼠肠系膜微循环障碍改善作用的实验研究[J].河北医药,2011,33(9)：1290-1293.
[6]孙余明,高关法,陆胜康.补阳还五汤胶囊对HFRS所致微循环障碍的临床观察[J].浙江中西医结合杂志,1998,8(5)：267-268.
[7]Pan, P., X. Zhang, et al. Effects of electro-acupuncture on endothelium-derived endothelin-1 and endothelial nitric oxide synthase of rats with hypoxia-induced pulmonary hypertension. Exp Biol Med (Maywood),2010,235(5):642-648.
[8]邱雪,洪铁,孟勤,等.人参皂苷单体Rb-1、Re及Rg-1对肾上腺素所致小鼠耳廓微循环障碍的改善作用[J].吉林大学学报(医学版),2009,35(2)：314-317.
[9]王巧云.黄芪注射液对血瘀证兔血液流变学的影响[J].中药药理与临床,2004,20(2)：19-20.
[10]王潇.三七三醇皂苷保护药物性肝损伤的研究[D].昆明：昆明理工大学,2009.
[11]张娴文,李凤贤,李辉.三七皂苷抗肝纤维化作用的现状[J].中国新药杂志,2007,16(4)：260-263.
[12]孙兰,刘世成,胡小鹰.三七保肝作用及其机理研究进展[J].中医药信息,2006,23(1)：17-19.
[13]Chen WX, Wang F, Liu YY, ex al. Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion [J]. World Journal of Gastroenterology,2008,14(1):29-37.
[14]黄荣柏,黄效廷,胡锡琮,等.经门静脉灌注丹参对肝硬变患者门静脉血流动力学的影响.广西医学,2005,27(1)：98-99.
[15]刘学民,刘青光,潘承恩,等.白藜芦醇治疗重症急性胰腺炎肺微循环障碍的研究.中华普通外科杂志,2004,19(4)：253-1-254.
[16]翁维良,工怡,马惠敏,等.20种活血药对血液粘滞性作用的比较观察[J].中医杂志,1984,(2)：69-71.
[17]韩晶岩,秋叶保忠,堀江义则,等.复方丹参滴丸及其主要成分丹参、三七对缺血再灌注引起的大鼠肠系膜微循环障碍的多环节改善作用[J].世界科学技术-中医药现代化,2008,(3)：99-105.
[18]赵乔,曲玲,游秋石,等.口服活血化癖药对小鼠软脑膜微循环的影响[J].中国微循环,2003,7(1)：27-28.
[19]周异群.复方桃仁承气口服液药理作用的研究.第七届全国中西医结合普通外科临床及基础研究学术会议,中国：天津,2001：261-264.
[20]郝二伟.平性药双向适用药性本质特征的研究[D].山东：山东中医药大学,2011.
[21]王福波,余安胜,曹艳杰.桃仁涂膜剂抗人源移植裸鼠肥厚性瘢痕的靶点研究[J].中华中医药学刊,2009,27(6)：1221-1224.
[22]钱冠清.血液流变学的病理生理意义与心脑血管病(上)[J].微循环学杂志,1995,5(3)：44-46.
[23]钱冠清.血液流变学的病理生理意义与心脑血管病(下)[J].微循环学杂志,1995,5(4)：44-46.
[24]赵艳明.桃仁红花药对对血瘀模型大鼠血液流变学的影响[D].黑龙江黑龙江中医药大学,2005.
[25]裴瑾,颜永刚,万德光,等.桃仁油对寒凝血瘀模型大鼠血液流变学及小鼠耳廓微循环的影响.第八届全国药用植物及植物药学术研讨会,中国：内蒙古呼和浩特,2009：22.
[26]杜晓霞.不同年龄段牦牛与成年黄牛肺微血管构筑特征的研究[D].甘肃：甘肃农业大学,2008.
[27]刘红.共聚焦激光显微内镜微血管成像对胃食管早期癌的诊断价值及其与肿瘤血管生成的相关性研究[D].山东：山东大学,2008.
[28]翁维良,工汀华,工怡,等.20种活血化瘀药对实验性微循环障碍影响的观察[J].中西医结合杂志.1984,4(9)：555-557.
[29]张清波,顾克仁,工玉润.用激光多普耳血流量仪及胆汁流量计测量桃仁提取物对肝脏微循环的影响[J].上海中医药杂志,1985,(7)：45-46.
[30]Ogino, K., T. Murakami, et al. Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion. Retina,2012, 32(1):77-85.
[31]Tsai, M., A. Kita, et al. In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J Clin Invest,2012,122(1):408-418.
[32]Lee, R. D., D. A. Barcel, et al. Pre-analytical and analytical variables affecting the measurement of plasma-derived microparticle tissue factor activity. Thromb Res,2012,129(1):80-85.
[33]Wolberg, A. S., M. M. Aleman, et al. Procoagulant activity in hemostasis and thrombosis:Virchow's triad revisited. Anesth Analg,2012,114(2):275-285.
[34]Vaquero-Puerta, C., E. M. San Norberto, et al. Shotgun wound and pellet embolism to the intracranial carotid artery." J Vasc Surg,2012,55(2):535-537.
[35]Qi, Z. X. and L. Chen. Effect of Chinese drugs for promoting blood circulation and eliminating blood stasis on vascular endothelial growth factor expression in rabbits with glucocorticoid-induced ischemic necrosis of femoral head. J Tradit Chin Med,2009,29(2):137-140.
[36]张金强,王付合,张方辉.桂枝茯苓丸加味治疗25例下肢血栓性静脉炎的临床观察.全国张仲景学术思想及医方应用研讨会,中国：河南南阳,2001：588-589.
[37]徐立,时乐,李祥,等.加减桃红四物汤醇提物对寒凝血瘀模型小鼠微循环和凝血时间的影响[J].江苏中医药,2008,40(11)：121-122.
[38]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].辽宁：辽宁中医药大学,2007.
[39]颜永刚.桃仁质量研究[D].成都：成都中医药大学,2008.
[40]运晨霞.桃仁总蛋白对荷瘤鼠细胞因子水平及肿瘤细胞凋亡影响的实验研究[D].黑龙江：黑龙江中医药大学,2003.
[1]Liu L, Shi GP. CD31:beyond a marker for endothelial cells [J]. Cardiovasc Res.,2012,94(1):3-5.
[2]Kim, S. J., J. S. Kim, et al. Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. Am J Pathol,2009,174(5): 1972-1980.
[3]Listi, F., C. Caruso, et al. PECAM-1/ CD31 in infarction and longevity. Ann N Y Acad Sci,2007,1100:132-139.
[4]Werner, N., S. Wassmann, et al. Circulating CD31+/annexin V+apoptotic micro particles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol,2006,26(1): 112-116.
[5]Carrithers, M., S. Tandon, et al. Enhanced susceptibility to endotoxic shock and impaired STAT3 signaling in CD31- deficient mice. Am J Pathol,2005, 166(1):185-196.
[6]Wong, C. W., G. Wiedle, et al. PECAM-1/CD31 trans-homophilic binding at the intercellular junctions is independent of its cytoplasmic domain, evidence for heterophilic interaction with integrin alphavbeta3 in Cist. Mol Biol Cell,2000,11(9):3109-3121.
[7]Bogen, S., J. Pak, et al. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med,1994,179(3):1059-1064.
[8]钱冠清.粘附分子的简介[J].微循环学杂志,1997,7(1)：5-7.
[9]钱冠清.主要科研进展,缺氧/再氧化时血管内皮细胞粘附分子ICAM-1的表达.巴德年主编.中国医学科学院中国协和医科大学年鉴,中国：天津,1997：55.
[10]钱冠清.血管内皮细胞粘附分子与心血管疾病[J].基础医学与临床,1999,19(3)：6-11.
[11]钱冠清.血管内皮细胞和动脉粥样硬化[J].微循环学杂志,2000,10(4)： 4-5.
[12]钱冠清,刘会齐,赵永革.ICAM-1在缺氧-再氧化引起的白细胞与内皮细胞粘附中的作用[J].中国医学科学院学报,1999,21(2)：130-134.
[13]钱冠清,刘会齐,刘晓辉.流体的不同流动方式对血管内皮细胞血管细胞粘附分子-1、核因子κB表达的影响[J].中国病理生理杂志,2002,18(7)：753-756.
[14]钱冠清,刘会齐,刘晓辉.流体切应力对血管内皮细胞粘附分子ICAM-1的影响[J].微循环学杂志,2000,10(3)：17-18.
[15]钱冠清,刘春华,刘会齐,等.TNF-a对内皮细胞粘附分子NFκB表达的影响[J].微循环学杂志,2000,10(3)：47-48.
[16]钱冠清,刘会齐,刘春华,等.不同有害因素对培养血管内皮细胞粘附分子及NFκB的影响[J].基础医学与临床,2002,22(6)：517-520.
[17]秦光明,金亚平,杨旭峰,等.ST段抬高型的心肌梗死患者外周血CD31+/CD42b-内皮微粒水平与心肌损伤指标的相关性[J].心脏杂志,2011,23(6)：835.
[18]赵庆娜,李侠,郭燕,等.老年人慢性左心力衰竭严重程度与循环内皮细胞微颗粒CD31+水平变化的关系[J].中国心血管杂志,2011,6(2)：112-114.
[19]郝二伟,邓家刚,杜正彩,等.平性药桃仁双向适用药性特征的研究[J].中药药理与临床,2011,27(1)：56-58.
[20]张秋雁,苏剑锋,周小青,等.桃仁及红花不同配比的血府逐瘀汤对大鼠急性心肌缺血和血液流变性的影响[J].中国临床康复,2005,9(3)：155-157.
[21]朱虹,王灿晖,杨进,等.桃仁承气汤对大鼠急性肾功能衰竭模型血液流变性及肾指数的影响[J].中国中医急症,2006,15(11)：1261-1263.
[22]赵艳明.桃仁红花药对对血瘀模型大鼠血液流变学的影响[D].黑龙江：黑龙江中医药大学,2005.
[23]Patil, A. S., R. B. Sable, et al. Occurrence, biochemical profile of vascular endothelial growth factor (VEGF) isoforms and their functions in endochondral ossification. J Cell Physiol,2012,227(4):1298-1308.
[24]Mackenzie, F. and C. Ruhrberg. Diverse roles for VEGF-A in the nervous system. Development,2012,139(8):1371-1380.
[25]Foehring, D., B. Brand-Saberi, et al. VEGF-Induced Growth Cone Enhancement Is Diminished by Inhibiting Tyrosine-Residue 1214 of VEGFR-2. Cells Tissues Organs, Mar 20,2012.
[26]Pennock, S. and A. Kazlauskas. VEGF-A competitively inhibits PDGF-dependent activation of PDGF receptor and subsequent signaling events and cellular responses. Mol Cell Biol, Mar 19,2012.
[27]Jansen, H., R. H. Meffert, et al. Detection of vascular endothelial growth factor (VEGF) in moderate osteoarthritis in a rabbit model. Ann Anat, Feb 25,2012.
[28]Ishijima, M., N. Suzuki, et al. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol, Mar 7,2012.
[29]Haberzettl, P., J. Lee, et al. Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-Induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow. Environ Health Perspect, Mar 14,2012.
[30]Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptor. Nature Medcine,2003,9:569-675.
[31]Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney lnt,2004,65: 2003-2017.
[32]Ruiz-Ortega M, Lorenzo O, Ruperez M, et al. Angiotensin Ⅱ activates nuclear transcription factor -KB through AT1 and AT2 in vascular smooth muscle cells:Molecular mechanisms. Circ Res,2000,86 (12):1266-1272.
[33]Datta K, Li J, Karumanchi SA, et al. Regulation of vascular permeability factor and vascular endothelial growth factor (VPF-VEGF-A) expression in podocytes. Kidney Int,2004,66:1471-1478.
[34]Kanellis J, Fraser S, Katerelos M, et al. Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells. Am J Physiol Renal Physiol,2000,278:905-915.
[35]Robert H, Abrahamson Dlt. Control of glomerular capillary development by growth factorlreceptor kinases. Pediatr Nephrol,2001,16:294-301.
[36]Kitamoto Y, Tolcunaga H, Miyamoto K, et al. VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant,2002, 17(suppl9):25-27.
[37]Masuda Y, Shimizu A, Mori, et al. Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis. Am J Pathol,2001,159: 599-608.
[38]Kelly DJ, Hepper C, Wu LL, et al. Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model. Nephrol Dial Transplant,2003,18:1286-1292.
[39]Kong DH, Anderson S, Kim YG, et al. Impaired angiogenesis in the aging kidney:vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis,2001,37:601-611.
[40]Seida A, Wada J, Morita Y, et al. Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion:does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? Am J Kidney Dis.2004,43:3-9.
[41]Choi K, Kennedy M, Kazarov A, et al. A common precursor for hematopoietic and endothelial cells. Development,1998,125:725-732.
[42]Kim BS, Chen J, Weinstein T, et al. VEGF expression in hypoxia and hyper-glycemia:reciprocal effect on branching angiogenesis in epithelial-endothelial co-cultures. J Am Soc Nephrol,2002,13:2027-2036.
[43]Kanellis J, Paizis K, Cox AJ, et al. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression. Kidney Int,2002,61:1696-1706.
[44]El Awad B, Kref B, Wolber EM, et al. Hypoxia and interleukin-stimulate vascular endothelial growth factor production in human proximal tubular cells. Kidney Int,2000,58:43-45.
[46]Chio YJ, Chakraborty S, Nguyen V, et al. Peritubulat capillary loss is associated with chronic tubuiointerst tial injury in human kidney:altered expression of vascular endothelial growth factor. Hum Pathol,2000,31: 1491-1497.
[47]齐振熙,陈磊.桃红四物汤对激素性股骨头缺血坏死模型兔血管内皮生长因子表达和血液流变学的影响[J].中国临床康复,2006,10(43)：70-72.
[48]齐振熙,陈磊.活血化瘀中药对激素性股骨头缺血坏死血管内皮生长因子表达的影响[J].中国骨伤,2007,20(9)：601-602.
[49]王轩,李引刚.桃仁、木香、黄芪分别与红花配伍对大鼠早期桡骨骨折愈合及VEGF表达的影响[J].山西中医学院学报,2009,10(3)：18-20.
[50]卢正华,张雨,宫丽鸿,等.桃核承气改良方对家兔血管内皮损伤后STAT3和VEGF影响的实验研究[J].中华中医药学刊,2009,27(5)：1022-1025.
[1]Eriksson, L., O. Erdogdu, et al. Effects of some anti-diabetic and cardio protective agents on proliferation and apoptosis of human coronary artery endothelial cells [J]. Cardiovasc Diabetol,2012,11(1):11-27.
[2]Wu, X., P. Chen, et al. A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis [J]. Int J Radiat Oncol Biol Phys. Mar 13,2012.
[3]Condorelli, R. A., A. E. Calogero, et al. Different profile of endothelial cell apoptosis in patients with Klinefelter's syndrome. J Endocrinol Invest, Mar 6,2012.
[4]Bakar, A. M., S. W. Park, et al. Isoflurane Protects Against Human Endothelial Cell Apoptosis by Inducing Sphingosine Kinase-1 via ERK MAPK. Int J Mol Sci.2012,13(1):977-993.
[5]Xing, Y. L., Z. Zhou, et al. Protocatechuic Aldehyde Inhibits Lipopolysaccharide-induced Human Umbilical Vein Endothelial Cell Apoptosis via Regulation of Caspase-3. Phytother Res. Feb 1,2012.
[6]Markelic, M., K. Velickovic, et al. Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia:the possible role of TNF-alpha. Eur J Histochem.2011,55(4):34.
[7]Zhu, X., A. Fu, et al. A high-throughput fluorescence resonance energy transfer (FRET)-based endothelial cell apoptosis assay and its application for screening vascular disrupting agents. Biochem Biophys Res Commun. 2012,418(4):641-646.
[8]金惠铭.细胞凋亡与微循环障碍[J].微循环学杂志,1997,7(1)：3-4.
[9]肾综合征出血热循环内皮细胞分离及其凋亡的临床研究[Z].应用技术,国际先进,山东省：济南市传染病医院,2011.
[10]马民.血瘀证形成的微观机理研究[D].济南：山东中医药大学,2003.
[11]农慧.川芎嗪促进BK-(Ca)通道介导早期糖尿病大鼠血管平滑肌细胞凋亡的研究[D].广州：广州中医药大学,2008.
[12]曹亚飞.中药骨康对破骨细胞活性及凋亡的影响[D].广州：广州中医药大学,2002.
[13]杨洪艳.中药治疗盆腔子宫内膜异位症的实验研究[D].广州：广州中医药大学,2001.
[14]刘颖.活血化瘀法治疗慢性肾小球肾炎的临床观察及相关性研究[D].长春：吉林大学,2006.
[15]姚楠.舒络粉针剂抗心肌缺血／再灌注损伤及作用机制研究[D].南京：南京中医药大学,2006.
[16]李鑫辉,黄政德,葛金文.加味丹参饮对血瘀证心肌缺血再灌注损伤家兔内皮细胞保护作用研究[J].中国药师,2011,14(1)：3-6.
[17]赵佐庆.大白鼠提睾肌缺血再灌注后血管内皮细胞的凋亡基因表达[J].第四军医大学学报,2001,22(14)：1339-1341.
[18]刘学民,刘青光,潘承恩,等.血管内皮凋亡对大鼠重症急性胰腺炎肺损伤的影响[J].第四军医大学学报,2003,24(18)：1677-1679.
[19]李媛媛.替罗非班在急性心肌梗死急诊介入治疗中对冠状动脉血流和内皮细胞功能的影响[D].济南：山东大学,2008.
[20]李丽君.定心方及丹参酮IIA防治心肌缺血—再灌注损伤的作用及机制研究[D].广州：南方医科大学,2010.
[21]裴卉.四逆汤对内毒素休克大鼠脑损伤保护的分子机制研究[D].北京：北京中医药大学,2009.
[22]夏培金.通络方剂对糖尿病大鼠视网膜病变的作用及机制研究[D].上海：第二军医大学,2007.
[23]童宗焰.内皮素在创伤性休克中作用的基础与临床研究[D].广州：第一军医大学,2005.
[24]丹参多酚酸盐治疗周围血管疾病的研究与开发[Z].基础理论,国内领先,上海市：中国科学院上海药物研究所,2009.
[25]王锦华,邱如卿.崩漏肾虚血瘀证与子宫内膜病理及细胞凋亡调控基因bax关系的研究[J].福建中医学院学报,2007,17(1)：3-5、23.
[26]呼健,杨明会,邓新立,等.补肾活血方对老年肾虚血瘀证患者CDllb/CD18、Bcl-2/Bax表达的影响[J].南方医科大学学报,2010,30(4)：760-762.
[27]荣晓凤,李荣亨,王维.气虚血瘀证大鼠血管平滑肌细胞bcl-2及bax相关凋亡因子的表达[J].中国老年学杂志,2010,30(5)：648-650.
[28]骆杰伟,邱明山,阮诗玮,等.狼疮性肾炎外周血淋巴细胞Fas、FasL、Bcl-2表达与血瘀证积分的关系[J].福建中医学院学报,2004,14(2)：7-9.
[22]马民.闭塞性动脉硬化症血瘀证患者bcl-2和HSP70基因的表达[J].云南大学学报(自然科学版),2004,26(6A)：1-5.
[23]王维,李荣亨,荣晓凤.复元胶囊对气虚血瘀证大鼠血管平滑肌细胞凋亡及凋亡相关基因表达的影响[J].中国新药杂志,2009,18(9)：838-843.
[24]尚建伟.人参皂甙对大鼠脊髓损伤后神经细胞凋亡及相关基因Bcl-2和Caspase-3表达的影响[D].汕头：汕头大学,2006.
[25]崔文瑶.丙泊酚对内毒素血症大鼠肾损伤的保护作用及机制研究[D].沈阳：中国医科大学,2009.
[26]葛益林.葛根素对豚鼠耳蜗缺血再灌注后细胞凋亡及相关蛋白表达的影响[D].长沙：中南大学,2006.
[27]杨戈,王阶,姜燕,等.复方丹参滴丸干预冠心病血瘀证凋亡相关基因的临床研究[A].第三届世界中西医结合大会,中国：广东广州,2007：708.
[28]马民,张桂娟.闭塞性动脉硬化症血瘀证患者bc1-2和HSP70基因的表达[J].辽宁中医杂志,2006,33(3)：260-262.
[29]张震宇,杨卫良,王立峰,等.断肢再植肌组织缺血再灌注损伤的细胞凋亡及Bax、Bcl-2表达[J].哈尔滨医科大学学报,2006,40(5)：371-374.
[30]刘晓梅.经颈内动脉注射质粒pLXSN-bcl-2 cDNA对大鼠脑缺血/再灌注损伤后神经细胞凋亡及MMP-9表达的影响[D].沈阳：中国医科大学,2006.
[31]王成果.Bax、Bcl-2和PAP-1在重症急性胰腺炎药物治疗中的作用和机制[D].西安：第四军医大学,2007.
[32]赵佐庆.大鼠提睾肌缺血再灌注损伤时血管平滑肌细胞和内皮细胞的增殖与凋亡[J].中国微循环,2002,6(1)：29-31.
[33]孔祥训.大肠癌中医辨证分型与外周血VEGF及P53基因表达水平的相关性研究[D].福建：福建中医药大学,2011.
[34]姜林.胃癌血瘀证与P53、C-erbB-2、VEGF表达的相关性研究[D].湖北：湖北中医学院,2008.
[35]刘起胜.乳腺癌中医辨证分型与GSTπ、P53表达的相关性分析[J].现代中西医结合杂志,2011,20(14)：1742-1743.
[36]刘永惠,郭少贤,常靖,等.丹参酮对血瘀证乳腺癌P53基因、mdm2基因表达的影响[J].陕西中医,2011,32(12)：1666-1667.
[37]崔同建,陈香莲,蒋云林,等.晚期大肠癌的病性证素与外周血P53、nm23的相关性研究[J].现代消化及介入诊疗,2011,16(4)：235-238.
[38]汪志霞.卵巢癌不同证型P-gp、P53的表达及亚砷酸、托泊替康等干预的体外研究[D].南京：南京中医药大学,2005.
[39]陈香莲.晚期大肠癌中医证素特点及其与血清肿瘤标志物及外周血P53、nm23的相关性研究[D].福州：福建中医药大学,2011.
[40]李净,胡建鹏,刘听,等.脑络欣通对脑缺血再灌注模型鼠神经细胞凋亡及P53蛋白表达的影响[J].安徽中医学院学报,2004,23(6)：20-22.
[41]陈建.血管内皮细胞hCASK-Id1通路对P53表达调控的机制研究[D].c重庆：第三军医大学,2007.
[1]Sha WC. Regulation of immune responses by NF kappa B/ Rel transcription factor [J]. Exp. Med.1998,187 (2):143-146.
[2]Wang D, Baldwin AS. Activation of nuclear factor-kappa B-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of ReIA/p65 on serine 529 [J]. Biol. Chem.1998,273 (45): 29411-29416.
[3]Haskill S, Beg AA, Tompkins SM, ex al. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell,1991,65(7):1281-1289.
[4]Thompson JE, Phillips RJ, Erdjument-Bromage H, ex al. IκBβ regulates the persistent response in a biphasic activation of NF-KB [J]. Cell,1995,80: 573-582.
[5]Whiteside ST, Israel A. I kappa B proteins:structure, function and regulation [J]. Semin. Cancer Biol.1997,8 (2):75-82.
[6]其其格.冠心病不稳定性心绞痛气虚血瘀证及炎症相关性研究[D].北京中医药大学：北京中医药大学,2010.
[7]常书福.冠状动脉微循环障碍的临床和实验研究[D].上海： 复旦大学,2010.
[8]顾大勇,曾祥元,马怖仁.NF-κB与微循环障碍[J].中国微循环,2001,5(1)：77-79.
[9]蒋素华.晚期缺血预适应对肾脏的保护作用及其机制研究[D].上海：复旦大学,2007.
[10]赵成广.内毒素诱导新生大鼠肾损害时肾组织NF-κB及TGF-β-1动态变化及其意义[D].沈阳：中国医科大学,2004.
[11]朱雅文.妊高征患者胎盘中NF-κB活化和母血TNF-α、ET及脐血TNF-α 含量变化的研究[D].郑州：郑州大学,2003.
[12]朱琳.危重病SIRS期患者中医证候研究及核因子-KB活化的临床意义[D].广州：广州中医药大学,2005.
[13]李永渝.核因子-κB作为急性胰腺炎治疗靶向的一些思考[A].第九届全国中西医结合普通外科学术交流大会暨胆道胰腺疾病新进展学习班论文汇编.[C].中国：杭州,2005：61-66.
[14]阚氏海,余崇林.NF-κB在重症急性胰腺炎肺损伤中的作用[J].泸州医学院学报,2007,30(4)：336-339.
[15]万涛.NF-κB、ICAM-1和炎症细胞因子在急性胰腺炎肝损伤中作用的实验研究[Z].国外医学临床生物化学与检验学分册,2005,26(12)：913-915.
[16]张喜平,金慧成,应荣超,等.黄芩甙对SAP大鼠多脏器细胞NF-κB表达的影响[Z].中国中西医结合外科杂志,2007,13(6)：550-554.
[17]Zhu, W., Q. Lv, et al. Protective Effect and Mechanism of Sodium Tanshinone ⅡA Sulfonate on Microcirculatory Disturbance of a-SM-actin Intestine in Rats with Sepsis [J]. Journal of Huazhong University of Science and Technology (Medical Sciences),2011,31 (4):441-445.
[18]刘雅,张海港,张翼冠,等.当归补血汤对气虚血瘀大鼠免疫功能及相关基因的调控[J].中药药理与临床,2009,25(5)：10-13.
[19]王玉德,崔勇,孙波.核因子-KB活化与重症急性胰腺炎微循环障碍的关系[J].中国交通医学杂志,2005,19(5)：431-432、435.
[20]郑健,吴群励,廖国华,等.益肾活血法治疗阿霉素肾病大鼠的实验研究[J].中国中西医结合杂志,2004,24(1)：124-128.
[21]张咏梅.室旁核内微量注射血管紧张素ⅡI对大鼠胃缺血—再灌注损伤的作用[D].杭州：浙江大学,2008.
[22]安尚玉.雌激素在缺氧／复氧心肌细胞中对NF-κB及粘附分子表达的影 响[D].长春：东北师范大学,2009.
[23]艾斯.益肾活血中药肾康灵干预小儿频复发性肾病与NF-κB、TXB-2、 6-keto-PGF-(1α)的临床研究[D].福州：福建中医学院,2008.
[24]郑健,吴群励,林青,等.肾康灵干预阿霉素肾病大鼠NF-κB的实验研究[J].福建中医学院学报,2005,15(2)：20-23.
[25]王升启,周喆,张红胜,等.复方丹参方治疗血瘀证的分子机理研究[A].中医药优秀论文选(下).[C].军事医学科学院放射与辐射医学研究所,2009：842-852.
[26]闫明先.氧化应激在胰腺纤维化中的作用及其分子机制的实验研究[D].济南：山东大学,2007.
[27]郑健,吴群励,林青,等.益肾活血中药肾康灵干预阿霉素肾病大鼠的药理研究[J].中国中西医结合肾病杂志,2004,5(10)：574-577.
[28]曾晓聪.替米沙坦对兔心肌缺血／再灌注损伤的影响[D].南宁：广西医科大学,2009.
[29]彭松林.参附注射液对肝脏缺血再灌注损伤中微循环障碍的影响[D].沈阳：中国医科大学,2005.
[30]王升启.复方丹参方治疗血瘀证的分子机理研究[Z].基础理论,国际先进,北京市：解放军军事医学科学院放射医学研究所,2005.12.30.
[31]郝旭亮.罗布麻总黄酮抗血栓作用物质基础及抗人脐静脉血管内皮细胞凋亡作用机理研究[D].太原：山西医科大学,2009.
[32]韩晶岩.内毒素引起的微循环障碍及中医药的改善作用[A].中国中西医结合学会微循环2009学术大会.[C].中国：浙江杭州,2009：4.
[33]黄政德,李鑫辉,张少泉,等.益气活血法对血瘀证兔缺血再灌注心肌细胞核因子κB蛋白表达影响[J].中华中医药学刊,2008,26(8)：1629-1631.
[34]张竞之,陈利国,胡小勤,等.黄芪多糖对原发性高血压病血瘀证患者Toll样受体4、核转录因子-KB表达的影响[J].中医杂志,2011,52(15)：1286-1289、1304.
[35]张竞之.黄芪多糖、丹皮酚对高血压病血瘀证内皮细胞损伤模型TLR4、 NF-κB表达的影响[D].广州：暨南大学,2009.
[36]陈敏.姜黄属中药及姜黄素活血化瘀抗动脉粥样硬化的文献整理及实验研究[D].北京：北京中医药大学,2011.
[37]韩笑,刘建勋,马晓斌,等.双参通冠方对急性心肌缺血再灌注NF-κB信号途径的影响[J].医学研究通讯,2004,33(11)：19-21.
[38]袁堂战,王卫星,陶绪雄,等.N-乙酰半胱氨酸联合维生素C对急性胰腺炎大鼠NF-κB和ICAM-1作用的实验研究[J].临床和实验医学杂志,2007,6(12)：17-19.
[39]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].沈阳：辽宁中医药大学,2007.
[40]李小波,李均,师晶丽.桃仁对单侧输尿管梗阻大鼠肾组织NF-kB、 TNF-α表达的影响[J].中国中医基础医学杂志,2006,12(7)：526-527.
[41]Baldwin AS Jr. The NF-kappa B and I kappa B proteins:new discoveries and insights [J]. Annu. Rev. Immunol.1996,14:649-683.
[42]Simeonidis S, Stauber D, Chen G, ex al. Mechanisms by which I kappa B proteins control NF-kappa B activity [J]. Proc. Natl. Acad. Sci. USA.1999, 96(1):49-54.
[43]May MJ, Ghosh S. Signal transduction through NF-kappa B [J]. Immunol. 1998,19 (2):80-88.
[44]Ohno H, Takimoto G, McKeithan TW. The candidate proto-oncogene Bcl-3 is related to genes implicated in cell lineage determination of cell cycle control [J]. Cell,1990,60:991-997.
[45]DiDonato JA, Hayakawa M, Rothwarf DM, ex al. A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B [J]. Nature,1997,388 (6642):548-554.
[1]Saha N, Moldovan F, Tardif G, et al. Interleukin-1 beta-converting enzyme/ Caspase-1 in human osteo-arthritic tissues:localization and role in the maturation of interleukin-1 beta and interleukin-18 [J]. Arthritis Rheum, 1999,42(8):1577-1587.
[2]Dinarello CA. Interleukin 1 and Interleukin 18 as mediators of inflammation and the aging process [J]. Am J Clin Nutr.2006,83(2):447-455.
[3]de Rivero JP, LotockiG, MarcilloAE, et al. A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury [J]. Neuroscience, 2008,28 (13):3404-3414.
[4]郭强,孔毅荣,付玲,等.炎性体的研究进展[J].军事医学科学院院刊,2007,31(5)：490-493。
[5]王萍.单核/巨噬细胞和vWF在慢性间质性肾炎肾组织上的表达及意义[D].中国医科大学：中国医科大学,2003.
[6]李建强.胆红素干预慢性阻塞性肺疾病和急性肺损伤的实验研究[Z].应用技术,国际先进,山西省：山西医科大学第二医院,2007.12.18.
[7]庞莹.ASC、caspase-1及IL-1p在牙周炎牙周组织中表达的动物实验研究[D].河北医科大学：河北医科大学,2010.
[8]Miural M, Zhu H, Nislow KH, et al. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death geneced-3 [J]. Cell,1993,75(4):653-660.
[9]Langford M P, McGee DJ, Ta KH, et al. Multiple Caspases mediate acute renal cell apoptosis induced by bacterial cell wall components [J]. RenFail, 2011,33(2):192-206.
[10]Chen P, Huang L, Zhang Y, et al. Anti-apoptotic effect of activated protein C on lipcpolysaccharide-slimulated human umbilical vein endothelial cells is associated with the inhibition of the Caspase-3 pathway [J]. MolMed Report,2010,3 (6):991-997.
[11]Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia [J]. Stroke,2009,40(5):331-339.
[12]沃兴德,丁志山.细胞凋亡与动脉粥样硬化[J].浙江中医学院学报,2001,25(2)：76-81.
[13]傅强,刘秉文.巨噬细胞、内皮细胞对高密度脂蛋白的氧化修饰[J].中国生物化学与分子生物学报,2001,17(5)：666-670.
[14]邱彦.Ox-LDL诱导单核／内皮细胞共培养系统VEGF上调及其促通透性升高的作用机制研究[D].第二军医大学：第二军医大学,2004.
[15]刘亮,刘旭盛,张晓启,等.巨噬细胞对血管内皮细胞增殖、Hoxb2、血管内皮生长因子受体和整合素αυβ3表达的影响[J].第一军医大学学报,2005,25(2)：148-151.
[16]刘亮.活化巨噬细胞对血管内皮细胞生物学特性及成血管作用的影响[D].第三军医大学：第三军医大学,2003.
[17]章必成,王俊,赵勇,等.替代性活化的巨噬细胞促进淋巴管内皮细胞增殖的机制[J].第四军医大学学报,2007,28(17)：1541-1543.
[18]章必成,王俊,赵勇,等.VEGF-C在替代性活化的巨噬细胞转分化为淋巴管内皮细胞中的作用[J].解放军医学杂志,2007,13(11)：1130-1133.
[19]章必成,王俊,赵勇,等.不同活化表型的巨噬细胞对淋巴管内皮细胞增殖、迁移和管样结构形成的影响[J].武汉大学学报(医学版),2007,28(3)：274-278.
[20]黄烨.冠心病血瘀证目标分子的鉴定、验证及功能分析[D].中国中医科学院：中国中医科学院,2011.
[21]徐拯.氢生理盐水对角叉菜胶诱导足肿胀的抗炎效应[D].第二军医大学：第二军医大学,2009.
[22]朱慧华,虞坚尔,张晓峰,等.平喘方对支气管哮喘模型小鼠巨噬细胞炎性蛋白-1α水平及CD86分子表达的实验研究[J].上海中医药杂志,2008,42(9)：58-62.
[23]赵志梅.补肾化瘀法治疗子宫内膜异位症不孕的研究[D].广州中医药大学：广州中医药大学,2000.
[24]黄朝义,朱兆荣,刘娟.桃红四物汤加减对母畜产后瘀血证疗效观察及药理初探[J].四川畜牧兽医学院学报,1994,8(4)：1-5.
[25]程青芳.防治泌乳期奶牛隐性乳房炎中草药的筛选及作用机理的研究[D].河北农业大学：河北农业大学,2002.
[1]Shepro D, M orel N M. Pericyte physiology [J]. FASEB,1993,7 (11):1031-1038.
[2]冯一梅,邹仲敏,徐辉.周细胞的研究进展[J].现代生物医学进展,2008,8(3)：571-589.
[3]王医术,李玉林,王心蕊,等.采用双重免疫组织化学及免疫电镜方法可将α-平滑肌肌动蛋白定位于乳腺癌间质新生血管周细胞[J].中国实验诊断学,2002,6(4)：203-205.
[4]王医术,李玉林,王心蕊,等.用a-SM-actin结合部位标记新生血管周细胞[J].吉林大学学报(医学版),2003,29(5)：594-598.
[5]程训民,江时森,马瑞,等.高血压合并糖尿病大鼠心肌毛细血管周细胞的观察[J].微循环学杂志,2008,18(1)：8-10.
[6]Patel, M. S., G. P. Taylor, et al. Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome." Am J Med Genet A, 2004,129A (3):294-299.
[7]Khourv J, Langeleben D. Platelet-activating factor stimulates lung pericyte growth in vitro. Am J Physiol,1996,270 (2):298-304.
[8]Khoury, J. and D. Langleben. Heparin-like molecules inhibit pulmonary vascular pericyte proliferation in vitro. Am J Physiol Lung Cell Mol Physiol,2000,279(2):L252-261.
[9]陈兰悦.AGE对DR周细胞的影响机制及银杏叶对DR的保护作用[D].长春：吉林大学,2004.
[10]倪劲松,王越晖,陈兰悦,等.银杏叶注射液对牛视网膜毛细血管周细胞的保护作用[J].吉林大学学报(医学版),2005,31(3)：368-371.
[11]Susan Olsona, Richard Oecklera, Xinmei Lia, et al. Angiotensin Ⅱ stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor. Am J Physaol Lung Cell Mol Physiol,2004,21:333-339.
[12]Klahr, S., and Morrissey, J. Angiotensin Ⅱ and gene expression m ladney. Am. J. Kidney Dis,1998,31:171-176.
[13]Marrero MB, Scheffer B, Paxton WC Heerdt L, et al. Direct stimulation of Jak/STAT pathway by the angiotensin Ⅱ AT1 receptor. Nature,1995,375: 247-250.
[14]Kodama Pan J, Makino S, Baba A, ex al. Angiotensin Ⅱ directly stimulates the JAK/STAT pathway through AT1 receptor in rat cardiomyocytes. Circulation,1996,94:401-405.
[15]Crawford DC, Chobanian AV, Brecher P. Angiotensin Ⅱ induces fibronechn expression associated with cardiac fibrosis in the rat. Circ Res.1994,74: 727-739.
[16]Sung CP, Arleth AJ, Storer BL, ex al. Angiotensin type 1 receptors mediate smooth muscle proliferation and endothelia biosynthesis in rat vascular smooth muscle [J]. Pharinacol Exp Then.1994,271:429-437.
[17]Imai T, Hirata Y, Emori T, ex al. Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells [J]. Hypertension,1992, 19:753-757.
[18]Arimura A, Asanuma F, Yagi H, ex al. Involvement of thromboxane A2 in bronchial hyperresponsiveness but not lung inflammation induced by bacterial lipopolysaccharide in guinea pigs. Eur J Pharmacol.1993,23: 13-21.
[19]Li P, Ferrario CM, Brosnihan KB. Losartan inhibits thromboxane A2-induced platelet aggregation and vascular constriction in spontaneously hypertensive rats. J Caxdtovasc Pharmacol.1998,198-205.
[20]Li P, Fukuhara M, Diz DI, ex al. Novel angiotensm Ⅱ AT (1) receptor antagonist irbesartan prevents thromboxane A (2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation. J Pharmacol Exp Ther.2000,292:238-246.
[21]李永荣,姚德厚,郭贵林,等.氟烷对慢性缺氧兔心肌p肾上腺素能受体的影响[J].中国应用生理学杂志,1996,12(1)：53-55.
[22]易岂建,钱永如,张远维.小儿慢性心力衰竭时血浆儿茶酚胺浓度及p-受体密度的改变[J].小儿急救医学杂志,1994,1(2)：76-78.
[23]冉光亮,仝识非,李永华,等.神经心源性晕厥患者血浆儿茶酚胺及红细胞膜p-受体的变化[J].临床心血管病杂志,2000,16(10)：457-458.
[24]尹智炜,史力生,陈志强,等.儿茶酚胺-p受体-cAMP系统在急性心肌梗死左室重塑中的生物学调控作用[J].中国老年学杂志,2006,26(4)：447-450.
[25]G.克劳斯.信号转导与调控的生物化学[M].北京：化学工业出版社,2005.
[26]Schutzer, W. E., H. Xue, et al. Effect of age on vascular beta2-adrenergic receptor desensitization is not mediated by the receptor coupling to Galphai proteins." J Gerontol A Biol Sci Med Sci,2006,61(9):899-906.
[27]Maeda, M., S. Kato, et al. Regulation of vascular smooth muscle proliferation and migration by beta2-chimaerin, a non-protein kinase C phorbol ester receptor. Int J Mol Med,2006,17(4):559-566.
[28]Dishy, V., G. G. Sofowora, et al. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med,2001,345(14):1030-1035.
[29]Eickelberg, O., M. Roth, et al. Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem, 1999,274(2):1005-1010.
[1]张静.中西医结合的微循环研究进展.微循环学杂志,2007,17(4)：1-7.
[2]Guo J, Sun K, Wang CS, et al. Protective effect s of dihydroxyl- phenyl lactic acid and salvianolic acid B on LPS- induced mesenter- ic microcirculatory disturbance in rat s. Shock,2008,29 (2):205-211.
[3]孙莉莎,吴航宇,徐江平,等.丹酚酸B对家兔血液流变性的影响.微循环学杂志,2003,13(1)：19-20.
[4]牛春雨,李继承,刘艳凯,等.夏至草醇提物对大鼠淋巴循环作用的实验研究.中国药学杂,2006,41(12)：914-917.
[5]张玉平,刘艳凯,姜华,等.夏至草生物碱对失血性休克大鼠淋巴微循环的影响.中国微循环,2006,10(3)：166-167.
[6]边永玲,刘正泉,牛春雨,等.夏至草醇提物对大鼠急性微循环障碍的影响.中国中西医结合急救杂志,2008,15(6)：338-341.
[7]于睿,兰宇.“以络论治”心肌微循环障碍.中华中医药学刊,2008,26(4)：828-829.
[8]陈士良,武效宏,王小冬.复方丹参注射液对缺血区冠脉循环的影响.中国医学研究与临床,2005,3(5)：13-1-16.
[9]赵娜,刘育英,卫晓红,等.复方丹参滴丸一次性预给药对缺血再灌注后大鼠心脏血流量和心肌损伤的改善作用.世界科学技术-中医药现代化,2008,10(3)：94-98.
[10]Xu XS, Ma ZZ, Wang F, et al. The Antioxidant cerebralcare granule (R) at tenuates cerebral microcirculatory disturbance during ischemia-reperfusion injury. Shock,2008,32 (2):201-209.
[11]徐想顺,王芳,刘育英,等.养血清脑颗粒对双侧颈动脉结扎-再通引起的蒙古沙鼠脑皮层微循环障碍和脑灌流量的改善作用.世界科学技术-中医药现代化,2008,10(3)：112-116.
[12]韩敏,薛茜,邹玉安,等.康脑液对脑缺血再灌注损伤大鼠软脑膜微循环的影响.中国微循环,2006,10(1)：22-25.
[13]韩敏,邹玉安,薛茜,等.康脑液对脑缺血再灌注损伤大鼠软脑膜微血流量的影响.中国临床康复,2006,10(23)：46-48.
[14]黄荣柏,黄效廷,胡锡琮,等.经门静脉灌注丹参对肝硬变患者门静脉血流动力学的影响.广西医学,2005,27(1)：98-99.
[15]Orie Y, Han J Y, Mori S, et al. Herbal cardiotonic pills prevent gut ischemia/ reperfusion- induced hepatic microvascular dysfunction in rats fed et hanol chronically. World J Gast roenterol,2005,11 (4):511-515.
[16]崔红燕,刘成,姜哲浩,等.扶正化瘀方对肝纤维化大鼠间质性基质金属蛋白酶活性的影响.上海中医药大学学报,2003,17(3)：35-38.
[17]谭春雨,谭善忠,蒋健,等.扶正化瘀方对肝纤维化大鼠肝脏明胶酶、TIMP-2和星状细胞凋亡的影响.上海中医药大学学报,2003,17(4)：40-44.
[18]Hen WX, Wang F, Liu YY, et al. Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gutischemia and reperfusion. World J Gast roenterol,2008,14 (1):29-37.
[19]刘学民,刘青光,潘承恩,等.白藜芦醇治疗重症急性胰腺炎肺微循环障碍的研究.中华普通外科杂志,2004,19(4)：253-1-254.
[20]赵桂峰,李竹庭,范英昌.丹酚酸B对缺氧再复氧心肌细胞内Ca2+浓度变化的影响.现代中西医结合杂志,2004,13(1)：19-20.
[21]宗刚军,陈景开,周辽军.银杏内酯B对体外培养乳鼠心肌细胞氧化损伤的保护作用.中国微循环,2004,8(4)：211-213.
[22]蒋丽敏,王雪峰,魏克伦,等.小柴胡汤对体外病毒性心肌炎模型的心肌细胞酶组织化学的影响.中华微生物学和免疫学杂志,2002,22(3)：298.
[23]郑世营,张晓膺,李虹,等.参附注射液对心肌细胞缺氧及缺氧／复氧Fas/ FasL表达的影响.中国急救医学,2005,25(12)：893-1-895.
[24]殷惠军,张颖,蒋路绒,等.西洋参叶总皂苷对急性心肌梗死大鼠心肌细胞凋亡及凋亡相关基因表达的影响.中国中西医结合杂志,2005,25(3)：232-235.
[25]王春玲,傅攀峰,李宏伟,等.葛根素对血管内皮细胞DNA损伤的保护作用.中国微循环,2004,8(6)：361-364.
[26]王怡,王少峡,姜志浩,等.首乌丹参方预处理对大鼠心肌缺血再灌注损伤iNOSmRNA表达的影响.辽宁中医杂志,2007,34(12)：1811-1814.
[27]王稳,徐标.丹参多酚酸盐对健康人血小板内皮型一氧化氮合酶活性的影响.中华高血压杂志,2007,15(7)：554-556.
[28]郑邦瑞,沈文律,文军,等.丹参注射液对重症急性胰腺炎大鼠胰腺NF-κB活化的影响.中国普外基础与临床杂志,2007,14(4)：392-395.
[29]刘建勋,韩笑,马晓斌,等.双参通冠方对急性心肌缺血再灌注模型核因子-KB信号途径及细胞间隙连接通讯的影响.中国中西医结合杂志,2005,25(3)：228-231.
[30]玉德,崔勇,孙波.核因子-κB活化与重症急性胰腺炎微循环障碍的关系.中国交通医学杂志,2005,19(5)：431-435.
[31]李石生,邓京振,赵守训,等.中药现代化研究的关键在于建立科学的现代中药理论体系——分子药性假说的提出[J].中国中西医结合杂志,2000,20(2)：83.
[32]欧阳兵,王振国,王鹏,等.“组群中药四性组合性效谱”假说及其论证[J].山东中医杂志,2006,25(3)：154.
[33]杨晓静,李和.桃仁油不皂化物与脂肪酸成分的分离与分析[J].农业与技术,2005,25(1)：84-86、90.
[34]杨晓静,李和.桃仁油不皂化物中甾醇和三萜醇的分离与鉴定[J].农业与技术,2005,25(2)：88-90、94.
[35]许惠玉,运晨霞,王雅贤.桃仁总蛋白对荷瘤鼠T淋巴细胞亚群及细胞凋亡的影响[J].齐齐哈尔医学院学报,2004,25(5)：485-487.
[36]潘会朝,秦文红.HPLC法测定苦杏仁和桃仁中苦杏仁甙的含量[J].世界最新医学信息文摘,2004,3(5)：1321-1322.
[2]王宏宇,胡大一.心脏和血管疾病的早期检测：功能性替代指标(上)[J].中国医刊,2006,41(2)：61-62.
[3]张世增,寇勇,郭娟,等.缺血性心脑血管病早期降纤治疗的疗效观察[J].现代预防医学,2003,30(1)：22-23.
[4]谢景荣,陈健,李敬兰,等.白细胞自发活化与粘附分子CDllb在高胆固醇血症中的应用[J].天津医科大学学报,2002,8(2)：149-150.
[5]热匹克,胡月明.心血管疾患合并甲襞微循环障碍性疾病应用蝮蛇抗栓酶治疗106例疗效观察[J].农垦医学,1999,21(1)：47-48.
[6]吴以岭.络病学概要[J].疑难病杂志,2004,3(1)：37-39.
[7]赵步长,庄欣.论心脑血管疾病的脑心同治原则[J].世界中医药,2006,3(1)37-39.
[8]陈奇.中药药理研究方法的发展概况与特点.中国药理学会第十次全国学术会议,中国天津,2009,247-252.
[9]王殿俊,刘小浩,金辉,等.热毒血瘀证动物模型的研究.江苏中医,1992,3：39-40.
[10]杨进,陆平成.家兔“热毒血癖证”系列动物模型的试制.南京中医药大学学报,1995,11(2)：70-72.
[11]邓家刚.一种瘀热互结证动物模型的建立方法[Z].医药评价,中医药理研究技术领域：CN101933951A,2011.01.05.
[12]Daniel De Backer, Gustavo Ospina-Tascon, Diamantino Salgado, ex al. Monitoring the microcirculation in the critically ill patient:current methods and future approaches [J].2010,36 (11):1813-1825.
[13]Trzeciak, S., J. V. McCoy, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med, 2008,34(12):2210-2217.
[14]Boldt, J. and C. Ince. The impact of fluid therapy on microcirculation and tissue oxygenation in hypovolemic patients:a review. Intensive Care Med, 2010,36(8):1299-1308.
[15]Creteur, J., D. De Backer, et al. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care,2006, Med 32(4):516-523.
[16]Boerma, E. C., M. A. Kuiper, et al. Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock:a prospective observational study. Intensive Care Med,2008,34(7):1294-1298.
[17]吴垦莉,张珊珊.寒凝血瘀证动物模型的研制[J].中国中医基础医学杂志,1996,2(2)：49-51.
[18]倪瑾,夏友详,张珊珊.寒凝血瘀与家兔血管关系的实验观察[J].微循环技术杂志,1996,(2)：96-98.
[19]郑小伟.寒凝血瘀证动物模型的量化研究[J].浙江中医学院学报,1999,23(2)：43-45.
[20]杨士友,孙备,裴月梅.风寒表证和寒凝血瘀证动物模型的研究[J].中国中医基础医学杂志,1997,3(1)：54-56.
[21]成秀梅,杜惠兰,李丹.寒凝血瘀证动物模型的创建[J].中国中医基础医学杂志,2005,11(8)：604-605.
[22]谢文光,马晓昌,邵宁生,等.赤芍治疗热毒血瘀证的血清蛋白质组变化的初步研究.中国中西医结合杂志,2005,25(6)：520-524.
[23]陈秋红,周小梅,多杰,等.青鹏胶囊解热镇痛及抗炎作用实验研究[J].山东中医杂志,2006,25(6)：407-409.
[24]魏陵博,彭敏,戎冬梅.通心络胶囊对角叉菜胶所致大鼠血栓形成的影响[J].中西医结合心脑血管病杂志,2006,9,4(9)：785-786.
[25]郭宏伟,邓家刚,郑作文,等.平性药对LPS所致淤热互结证大鼠微循环的影响[J].时珍国医国药,2011,22(4)：838-839.
[26]田牛,李玉珍,刘育英.血瘀证的微循环研究[J].中国中西医结合杂志,2001,21(4)：248-251.
[27]刘育英编著.微循环图谱.北京：人民军医出版社,2005：1-178.
[28]郭淑贞.血瘀证(心肌缺血)动物模型及其相关蛋白质组学研究[D].北京中医药大学：北京中医药大学,2007.
[29]姜智浩,王怡,范祥,等.血瘀证动物模型舌体动脉血管形态研究[J].辽宁中医杂志,2008,35(7)：1098-1099.
[30]张斌,王中华,王江蓉,等.血瘀型肝纤维化大鼠模型的建立与评价[J].中国中医基础医学杂志,2006,12(11)：836-838.
[31]王淑娟,王建中.血液流变学检验及其临床应用[J].中国医刊,2003,38(4)：215～216.
[32]俞纯山.血流变学研究进展及其临床应用[J].实用医学杂志,2002,18(5)：49～450.
[33]胡小勤.高血压病血瘀证血管内皮细胞损伤模型的研究[D].暨南大学：暨南大学,2007.
[34]Hertig, A. and E. Rondeau. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury. J Am Soc Nephrol,2004,15(4):844-853.
[35]席春生,孙雪峰,陈香关,等.调控纤维蛋自水平对不同鼠龄肾脏炎症反应的影响.中华老年医学杂志.2005,24(15)：365.
[36]肇启春.瓜蒌皮注射液对血瘀证模型大鼠血液流变学及血管内皮素的影响[D].大连：大连医科大学,2007.
[37]金末淑.艾灸膈俞穴对寒凝血瘀证模型大鼠血液流变学的实验研究[D].北京：北京中医药大学,2009.
[38]马小娜.病证结合子宫内膜异位症大鼠模型的建立与评价[D].北京中医药大学：北京中医药大学,2011.
[39]李春阳,李林,魏海峰,等.局灶性脑缺血大鼠血瘀证相关指标和脑损伤病理生理的动态变化[J].中国中西医结合急救杂志,2007,(5)：259-263.
[40]王巧云.黄芪注射液对血瘀证兔血液流变学的影响[J].中药药理与临床,2004,(2)：19-20.
[41]杨超,周岩,孙晓红,等.具有中医“热毒血瘀证”表征的大鼠血液成分和流变学变化[J].中国比较医学杂志,2007,(10)：607-612.
[42]田牛.主要器官微循环的特点及其改变[J].微循环技术杂志,1995,(1)：41-50.
[43]田牛,胡金麟.临床微循环观测结果的数学表达[J].中国生物医学工程学报,1996,(1)：14-17.
[44]田牛,姜澜.临床微循环“综合定量评价”理论基础的再认识[J].微循环学杂志,1994,(2)：l-3.
[45]田牛.加快我国临床微循环的发展[J].中国微循环,1998,(1)：50-53.
[46]秦任甲.动脉粥样硬化好发部位血液流态和参数分析[J].中国医学物理学杂志,2009,26(2)：1102-1104.
[47]李静,冯建涛,孙全梅,等.血管功能界面微纳尺度形貌的表征与仿生制备[J].微循环学杂志,2011,(2)：80.
[48]张英骏,钱冠清.显微电视在微循环中的应用[J].医学研究通讯,1982,(6)：27.
[49]金惠铭.应用多功能显微图象测量仪测量微血管管径、流速和数目[J].上海第一医学院学报,1985,(5)：395-396.
[50]胡金麟.基于灰度的微血管管径自跟踪算法[J].中国生物医学工程学报,1998,(2)：78-81、91.
[51]钱冠清.各种止血因子在血栓诊断中的作用[J].国外医学参考资料(内科学分册),1974,(11)：492-494.
[52]张云芳.活血止痛液对小鼠凝血时间及微循环影响的实验研究[J].中医正骨,1999,11(12)：16.
[53]贾振华.血管内皮细胞结构及其功能变化与血瘀证形成关系的研究[D].山东：山东中医药大学,2002.
[54]胡建鹏.益气活血法对脑缺血再灌注大鼠神经细胞凋亡Fas/FasL信号转导通路与调控的研究[D].北京：北京中医药大学,2004.
[55]林兰,王波,魏海峰,等.低能量He-Ne激光对实验性家兔糖尿病脑梗塞皮层脑微循环的影响[J].中国中医药信息杂志,2002,9(2)：24-26.
[56]Gules, I., M. Satoh, et al. Comparison of three rat models of cerebral vasospasm. Am J Physiol Heart Circ Physiol,2002,283(6):H2551-2559.
[57]张俊杰,刘茜,张磊,等.丹参对微循环障碍的调节作用[J].中国微循环,2002,6(5)：316.
[58]滕久祥,彭芝配,郭建生,等.九气拈痛胶囊对大鼠“寒凝血瘀”模型的影响[J].新中医,1998,30(11)：32-33.
[59]张清波,顾克仁,王玉润.用激光多普耳血流量仪及胆汁流量计测定桃仁提取物对肝脏微循环的影响.[J]上海中医药杂志,1985,7：45-46.
[1]王世军,姬广臣,史仁华,等.葛根素、川芎嗪、丹参注射液对大脑中动脉阻断大鼠脑微循环血流量的影响[J].中成药,2000,22(6)：38-40.
[2]Han, J. Y., Y. Horie, et al. Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery. World J Gastroenterol,2007,13(26):3581-3591.
[3]李俊杰,赵自刚,牛春雨,等.夏至草醇提物对急性微循环障碍大鼠一氧化氮及其合酶的影响[J].微循环学杂志,2007,17(3)：27-28、30、80、82-83.
[4]李俊杰,王伟平,赵自刚,等.夏至草醇提物对急性微循环障碍大鼠自由基损伤的影响[J].中国微循环,2007,11(5)：300-302.
[5]杨淼,刘玉玉,李淑娟.黄芪注射液对内毒素诱导大鼠肠系膜微循环障碍改善作用的实验研究[J].河北医药,2011,33(9)：1290-1293.
[6]孙余明,高关法,陆胜康.补阳还五汤胶囊对HFRS所致微循环障碍的临床观察[J].浙江中西医结合杂志,1998,8(5)：267-268.
[7]Pan, P., X. Zhang, et al. Effects of electro-acupuncture on endothelium-derived endothelin-1 and endothelial nitric oxide synthase of rats with hypoxia-induced pulmonary hypertension. Exp Biol Med (Maywood),2010,235(5):642-648.
[8]邱雪,洪铁,孟勤,等.人参皂苷单体Rb-1、Re及Rg-1对肾上腺素所致小鼠耳廓微循环障碍的改善作用[J].吉林大学学报(医学版),2009,35(2)：314-317.
[9]王巧云.黄芪注射液对血瘀证兔血液流变学的影响[J].中药药理与临床,2004,20(2)：19-20.
[10]王潇.三七三醇皂苷保护药物性肝损伤的研究[D].昆明：昆明理工大学,2009.
[11]张娴文,李凤贤,李辉.三七皂苷抗肝纤维化作用的现状[J].中国新药杂志,2007,16(4)：260-263.
[12]孙兰,刘世成,胡小鹰.三七保肝作用及其机理研究进展[J].中医药信息,2006,23(1)：17-19.
[13]Chen WX, Wang F, Liu YY, ex al. Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion [J]. World Journal of Gastroenterology,2008,14(1):29-37.
[14]黄荣柏,黄效廷,胡锡琮,等.经门静脉灌注丹参对肝硬变患者门静脉血流动力学的影响.广西医学,2005,27(1)：98-99.
[15]刘学民,刘青光,潘承恩,等.白藜芦醇治疗重症急性胰腺炎肺微循环障碍的研究.中华普通外科杂志,2004,19(4)：253-1-254.
[16]翁维良,工怡,马惠敏,等.20种活血药对血液粘滞性作用的比较观察[J].中医杂志,1984,(2)：69-71.
[17]韩晶岩,秋叶保忠,堀江义则,等.复方丹参滴丸及其主要成分丹参、三七对缺血再灌注引起的大鼠肠系膜微循环障碍的多环节改善作用[J].世界科学技术-中医药现代化,2008,(3)：99-105.
[18]赵乔,曲玲,游秋石,等.口服活血化癖药对小鼠软脑膜微循环的影响[J].中国微循环,2003,7(1)：27-28.
[19]周异群.复方桃仁承气口服液药理作用的研究.第七届全国中西医结合普通外科临床及基础研究学术会议,中国：天津,2001：261-264.
[20]郝二伟.平性药双向适用药性本质特征的研究[D].山东：山东中医药大学,2011.
[21]王福波,余安胜,曹艳杰.桃仁涂膜剂抗人源移植裸鼠肥厚性瘢痕的靶点研究[J].中华中医药学刊,2009,27(6)：1221-1224.
[22]钱冠清.血液流变学的病理生理意义与心脑血管病(上)[J].微循环学杂志,1995,5(3)：44-46.
[23]钱冠清.血液流变学的病理生理意义与心脑血管病(下)[J].微循环学杂志,1995,5(4)：44-46.
[24]赵艳明.桃仁红花药对对血瘀模型大鼠血液流变学的影响[D].黑龙江黑龙江中医药大学,2005.
[25]裴瑾,颜永刚,万德光,等.桃仁油对寒凝血瘀模型大鼠血液流变学及小鼠耳廓微循环的影响.第八届全国药用植物及植物药学术研讨会,中国：内蒙古呼和浩特,2009：22.
[26]杜晓霞.不同年龄段牦牛与成年黄牛肺微血管构筑特征的研究[D].甘肃：甘肃农业大学,2008.
[27]刘红.共聚焦激光显微内镜微血管成像对胃食管早期癌的诊断价值及其与肿瘤血管生成的相关性研究[D].山东：山东大学,2008.
[28]翁维良,工汀华,工怡,等.20种活血化瘀药对实验性微循环障碍影响的观察[J].中西医结合杂志.1984,4(9)：555-557.
[29]张清波,顾克仁,工玉润.用激光多普耳血流量仪及胆汁流量计测量桃仁提取物对肝脏微循环的影响[J].上海中医药杂志,1985,(7)：45-46.
[30]Ogino, K., T. Murakami, et al. Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion. Retina,2012, 32(1):77-85.
[31]Tsai, M., A. Kita, et al. In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J Clin Invest,2012,122(1):408-418.
[32]Lee, R. D., D. A. Barcel, et al. Pre-analytical and analytical variables affecting the measurement of plasma-derived microparticle tissue factor activity. Thromb Res,2012,129(1):80-85.
[33]Wolberg, A. S., M. M. Aleman, et al. Procoagulant activity in hemostasis and thrombosis:Virchow's triad revisited. Anesth Analg,2012,114(2):275-285.
[34]Vaquero-Puerta, C., E. M. San Norberto, et al. Shotgun wound and pellet embolism to the intracranial carotid artery." J Vasc Surg,2012,55(2):535-537.
[35]Qi, Z. X. and L. Chen. Effect of Chinese drugs for promoting blood circulation and eliminating blood stasis on vascular endothelial growth factor expression in rabbits with glucocorticoid-induced ischemic necrosis of femoral head. J Tradit Chin Med,2009,29(2):137-140.
[36]张金强,王付合,张方辉.桂枝茯苓丸加味治疗25例下肢血栓性静脉炎的临床观察.全国张仲景学术思想及医方应用研讨会,中国：河南南阳,2001：588-589.
[37]徐立,时乐,李祥,等.加减桃红四物汤醇提物对寒凝血瘀模型小鼠微循环和凝血时间的影响[J].江苏中医药,2008,40(11)：121-122.
[38]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].辽宁：辽宁中医药大学,2007.
[39]颜永刚.桃仁质量研究[D].成都：成都中医药大学,2008.
[40]运晨霞.桃仁总蛋白对荷瘤鼠细胞因子水平及肿瘤细胞凋亡影响的实验研究[D].黑龙江：黑龙江中医药大学,2003.
[1]Liu L, Shi GP. CD31:beyond a marker for endothelial cells [J]. Cardiovasc Res.,2012,94(1):3-5.
[2]Kim, S. J., J. S. Kim, et al. Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. Am J Pathol,2009,174(5): 1972-1980.
[3]Listi, F., C. Caruso, et al. PECAM-1/ CD31 in infarction and longevity. Ann N Y Acad Sci,2007,1100:132-139.
[4]Werner, N., S. Wassmann, et al. Circulating CD31+/annexin V+apoptotic micro particles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol,2006,26(1): 112-116.
[5]Carrithers, M., S. Tandon, et al. Enhanced susceptibility to endotoxic shock and impaired STAT3 signaling in CD31- deficient mice. Am J Pathol,2005, 166(1):185-196.
[6]Wong, C. W., G. Wiedle, et al. PECAM-1/CD31 trans-homophilic binding at the intercellular junctions is independent of its cytoplasmic domain, evidence for heterophilic interaction with integrin alphavbeta3 in Cist. Mol Biol Cell,2000,11(9):3109-3121.
[7]Bogen, S., J. Pak, et al. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med,1994,179(3):1059-1064.
[8]钱冠清.粘附分子的简介[J].微循环学杂志,1997,7(1)：5-7.
[9]钱冠清.主要科研进展,缺氧/再氧化时血管内皮细胞粘附分子ICAM-1的表达.巴德年主编.中国医学科学院中国协和医科大学年鉴,中国：天津,1997：55.
[10]钱冠清.血管内皮细胞粘附分子与心血管疾病[J].基础医学与临床,1999,19(3)：6-11.
[11]钱冠清.血管内皮细胞和动脉粥样硬化[J].微循环学杂志,2000,10(4)： 4-5.
[12]钱冠清,刘会齐,赵永革.ICAM-1在缺氧-再氧化引起的白细胞与内皮细胞粘附中的作用[J].中国医学科学院学报,1999,21(2)：130-134.
[13]钱冠清,刘会齐,刘晓辉.流体的不同流动方式对血管内皮细胞血管细胞粘附分子-1、核因子κB表达的影响[J].中国病理生理杂志,2002,18(7)：753-756.
[14]钱冠清,刘会齐,刘晓辉.流体切应力对血管内皮细胞粘附分子ICAM-1的影响[J].微循环学杂志,2000,10(3)：17-18.
[15]钱冠清,刘春华,刘会齐,等.TNF-a对内皮细胞粘附分子NFκB表达的影响[J].微循环学杂志,2000,10(3)：47-48.
[16]钱冠清,刘会齐,刘春华,等.不同有害因素对培养血管内皮细胞粘附分子及NFκB的影响[J].基础医学与临床,2002,22(6)：517-520.
[17]秦光明,金亚平,杨旭峰,等.ST段抬高型的心肌梗死患者外周血CD31+/CD42b-内皮微粒水平与心肌损伤指标的相关性[J].心脏杂志,2011,23(6)：835.
[18]赵庆娜,李侠,郭燕,等.老年人慢性左心力衰竭严重程度与循环内皮细胞微颗粒CD31+水平变化的关系[J].中国心血管杂志,2011,6(2)：112-114.
[19]郝二伟,邓家刚,杜正彩,等.平性药桃仁双向适用药性特征的研究[J].中药药理与临床,2011,27(1)：56-58.
[20]张秋雁,苏剑锋,周小青,等.桃仁及红花不同配比的血府逐瘀汤对大鼠急性心肌缺血和血液流变性的影响[J].中国临床康复,2005,9(3)：155-157.
[21]朱虹,王灿晖,杨进,等.桃仁承气汤对大鼠急性肾功能衰竭模型血液流变性及肾指数的影响[J].中国中医急症,2006,15(11)：1261-1263.
[22]赵艳明.桃仁红花药对对血瘀模型大鼠血液流变学的影响[D].黑龙江：黑龙江中医药大学,2005.
[23]Patil, A. S., R. B. Sable, et al. Occurrence, biochemical profile of vascular endothelial growth factor (VEGF) isoforms and their functions in endochondral ossification. J Cell Physiol,2012,227(4):1298-1308.
[24]Mackenzie, F. and C. Ruhrberg. Diverse roles for VEGF-A in the nervous system. Development,2012,139(8):1371-1380.
[25]Foehring, D., B. Brand-Saberi, et al. VEGF-Induced Growth Cone Enhancement Is Diminished by Inhibiting Tyrosine-Residue 1214 of VEGFR-2. Cells Tissues Organs, Mar 20,2012.
[26]Pennock, S. and A. Kazlauskas. VEGF-A competitively inhibits PDGF-dependent activation of PDGF receptor and subsequent signaling events and cellular responses. Mol Cell Biol, Mar 19,2012.
[27]Jansen, H., R. H. Meffert, et al. Detection of vascular endothelial growth factor (VEGF) in moderate osteoarthritis in a rabbit model. Ann Anat, Feb 25,2012.
[28]Ishijima, M., N. Suzuki, et al. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol, Mar 7,2012.
[29]Haberzettl, P., J. Lee, et al. Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-Induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow. Environ Health Perspect, Mar 14,2012.
[30]Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptor. Nature Medcine,2003,9:569-675.
[31]Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney lnt,2004,65: 2003-2017.
[32]Ruiz-Ortega M, Lorenzo O, Ruperez M, et al. Angiotensin Ⅱ activates nuclear transcription factor -KB through AT1 and AT2 in vascular smooth muscle cells:Molecular mechanisms. Circ Res,2000,86 (12):1266-1272.
[33]Datta K, Li J, Karumanchi SA, et al. Regulation of vascular permeability factor and vascular endothelial growth factor (VPF-VEGF-A) expression in podocytes. Kidney Int,2004,66:1471-1478.
[34]Kanellis J, Fraser S, Katerelos M, et al. Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells. Am J Physiol Renal Physiol,2000,278:905-915.
[35]Robert H, Abrahamson Dlt. Control of glomerular capillary development by growth factorlreceptor kinases. Pediatr Nephrol,2001,16:294-301.
[36]Kitamoto Y, Tolcunaga H, Miyamoto K, et al. VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant,2002, 17(suppl9):25-27.
[37]Masuda Y, Shimizu A, Mori, et al. Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis. Am J Pathol,2001,159: 599-608.
[38]Kelly DJ, Hepper C, Wu LL, et al. Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model. Nephrol Dial Transplant,2003,18:1286-1292.
[39]Kong DH, Anderson S, Kim YG, et al. Impaired angiogenesis in the aging kidney:vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis,2001,37:601-611.
[40]Seida A, Wada J, Morita Y, et al. Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion:does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? Am J Kidney Dis.2004,43:3-9.
[41]Choi K, Kennedy M, Kazarov A, et al. A common precursor for hematopoietic and endothelial cells. Development,1998,125:725-732.
[42]Kim BS, Chen J, Weinstein T, et al. VEGF expression in hypoxia and hyper-glycemia:reciprocal effect on branching angiogenesis in epithelial-endothelial co-cultures. J Am Soc Nephrol,2002,13:2027-2036.
[43]Kanellis J, Paizis K, Cox AJ, et al. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression. Kidney Int,2002,61:1696-1706.
[44]El Awad B, Kref B, Wolber EM, et al. Hypoxia and interleukin-stimulate vascular endothelial growth factor production in human proximal tubular cells. Kidney Int,2000,58:43-45.
[46]Chio YJ, Chakraborty S, Nguyen V, et al. Peritubulat capillary loss is associated with chronic tubuiointerst tial injury in human kidney:altered expression of vascular endothelial growth factor. Hum Pathol,2000,31: 1491-1497.
[47]齐振熙,陈磊.桃红四物汤对激素性股骨头缺血坏死模型兔血管内皮生长因子表达和血液流变学的影响[J].中国临床康复,2006,10(43)：70-72.
[48]齐振熙,陈磊.活血化瘀中药对激素性股骨头缺血坏死血管内皮生长因子表达的影响[J].中国骨伤,2007,20(9)：601-602.
[49]王轩,李引刚.桃仁、木香、黄芪分别与红花配伍对大鼠早期桡骨骨折愈合及VEGF表达的影响[J].山西中医学院学报,2009,10(3)：18-20.
[50]卢正华,张雨,宫丽鸿,等.桃核承气改良方对家兔血管内皮损伤后STAT3和VEGF影响的实验研究[J].中华中医药学刊,2009,27(5)：1022-1025.
[1]Eriksson, L., O. Erdogdu, et al. Effects of some anti-diabetic and cardio protective agents on proliferation and apoptosis of human coronary artery endothelial cells [J]. Cardiovasc Diabetol,2012,11(1):11-27.
[2]Wu, X., P. Chen, et al. A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis [J]. Int J Radiat Oncol Biol Phys. Mar 13,2012.
[3]Condorelli, R. A., A. E. Calogero, et al. Different profile of endothelial cell apoptosis in patients with Klinefelter's syndrome. J Endocrinol Invest, Mar 6,2012.
[4]Bakar, A. M., S. W. Park, et al. Isoflurane Protects Against Human Endothelial Cell Apoptosis by Inducing Sphingosine Kinase-1 via ERK MAPK. Int J Mol Sci.2012,13(1):977-993.
[5]Xing, Y. L., Z. Zhou, et al. Protocatechuic Aldehyde Inhibits Lipopolysaccharide-induced Human Umbilical Vein Endothelial Cell Apoptosis via Regulation of Caspase-3. Phytother Res. Feb 1,2012.
[6]Markelic, M., K. Velickovic, et al. Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia:the possible role of TNF-alpha. Eur J Histochem.2011,55(4):34.
[7]Zhu, X., A. Fu, et al. A high-throughput fluorescence resonance energy transfer (FRET)-based endothelial cell apoptosis assay and its application for screening vascular disrupting agents. Biochem Biophys Res Commun. 2012,418(4):641-646.
[8]金惠铭.细胞凋亡与微循环障碍[J].微循环学杂志,1997,7(1)：3-4.
[9]肾综合征出血热循环内皮细胞分离及其凋亡的临床研究[Z].应用技术,国际先进,山东省：济南市传染病医院,2011.
[10]马民.血瘀证形成的微观机理研究[D].济南：山东中医药大学,2003.
[11]农慧.川芎嗪促进BK-(Ca)通道介导早期糖尿病大鼠血管平滑肌细胞凋亡的研究[D].广州：广州中医药大学,2008.
[12]曹亚飞.中药骨康对破骨细胞活性及凋亡的影响[D].广州：广州中医药大学,2002.
[13]杨洪艳.中药治疗盆腔子宫内膜异位症的实验研究[D].广州：广州中医药大学,2001.
[14]刘颖.活血化瘀法治疗慢性肾小球肾炎的临床观察及相关性研究[D].长春：吉林大学,2006.
[15]姚楠.舒络粉针剂抗心肌缺血／再灌注损伤及作用机制研究[D].南京：南京中医药大学,2006.
[16]李鑫辉,黄政德,葛金文.加味丹参饮对血瘀证心肌缺血再灌注损伤家兔内皮细胞保护作用研究[J].中国药师,2011,14(1)：3-6.
[17]赵佐庆.大白鼠提睾肌缺血再灌注后血管内皮细胞的凋亡基因表达[J].第四军医大学学报,2001,22(14)：1339-1341.
[18]刘学民,刘青光,潘承恩,等.血管内皮凋亡对大鼠重症急性胰腺炎肺损伤的影响[J].第四军医大学学报,2003,24(18)：1677-1679.
[19]李媛媛.替罗非班在急性心肌梗死急诊介入治疗中对冠状动脉血流和内皮细胞功能的影响[D].济南：山东大学,2008.
[20]李丽君.定心方及丹参酮IIA防治心肌缺血—再灌注损伤的作用及机制研究[D].广州：南方医科大学,2010.
[21]裴卉.四逆汤对内毒素休克大鼠脑损伤保护的分子机制研究[D].北京：北京中医药大学,2009.
[22]夏培金.通络方剂对糖尿病大鼠视网膜病变的作用及机制研究[D].上海：第二军医大学,2007.
[23]童宗焰.内皮素在创伤性休克中作用的基础与临床研究[D].广州：第一军医大学,2005.
[24]丹参多酚酸盐治疗周围血管疾病的研究与开发[Z].基础理论,国内领先,上海市：中国科学院上海药物研究所,2009.
[25]王锦华,邱如卿.崩漏肾虚血瘀证与子宫内膜病理及细胞凋亡调控基因bax关系的研究[J].福建中医学院学报,2007,17(1)：3-5、23.
[26]呼健,杨明会,邓新立,等.补肾活血方对老年肾虚血瘀证患者CDllb/CD18、Bcl-2/Bax表达的影响[J].南方医科大学学报,2010,30(4)：760-762.
[27]荣晓凤,李荣亨,王维.气虚血瘀证大鼠血管平滑肌细胞bcl-2及bax相关凋亡因子的表达[J].中国老年学杂志,2010,30(5)：648-650.
[28]骆杰伟,邱明山,阮诗玮,等.狼疮性肾炎外周血淋巴细胞Fas、FasL、Bcl-2表达与血瘀证积分的关系[J].福建中医学院学报,2004,14(2)：7-9.
[22]马民.闭塞性动脉硬化症血瘀证患者bcl-2和HSP70基因的表达[J].云南大学学报(自然科学版),2004,26(6A)：1-5.
[23]王维,李荣亨,荣晓凤.复元胶囊对气虚血瘀证大鼠血管平滑肌细胞凋亡及凋亡相关基因表达的影响[J].中国新药杂志,2009,18(9)：838-843.
[24]尚建伟.人参皂甙对大鼠脊髓损伤后神经细胞凋亡及相关基因Bcl-2和Caspase-3表达的影响[D].汕头：汕头大学,2006.
[25]崔文瑶.丙泊酚对内毒素血症大鼠肾损伤的保护作用及机制研究[D].沈阳：中国医科大学,2009.
[26]葛益林.葛根素对豚鼠耳蜗缺血再灌注后细胞凋亡及相关蛋白表达的影响[D].长沙：中南大学,2006.
[27]杨戈,王阶,姜燕,等.复方丹参滴丸干预冠心病血瘀证凋亡相关基因的临床研究[A].第三届世界中西医结合大会,中国：广东广州,2007：708.
[28]马民,张桂娟.闭塞性动脉硬化症血瘀证患者bc1-2和HSP70基因的表达[J].辽宁中医杂志,2006,33(3)：260-262.
[29]张震宇,杨卫良,王立峰,等.断肢再植肌组织缺血再灌注损伤的细胞凋亡及Bax、Bcl-2表达[J].哈尔滨医科大学学报,2006,40(5)：371-374.
[30]刘晓梅.经颈内动脉注射质粒pLXSN-bcl-2 cDNA对大鼠脑缺血/再灌注损伤后神经细胞凋亡及MMP-9表达的影响[D].沈阳：中国医科大学,2006.
[31]王成果.Bax、Bcl-2和PAP-1在重症急性胰腺炎药物治疗中的作用和机制[D].西安：第四军医大学,2007.
[32]赵佐庆.大鼠提睾肌缺血再灌注损伤时血管平滑肌细胞和内皮细胞的增殖与凋亡[J].中国微循环,2002,6(1)：29-31.
[33]孔祥训.大肠癌中医辨证分型与外周血VEGF及P53基因表达水平的相关性研究[D].福建：福建中医药大学,2011.
[34]姜林.胃癌血瘀证与P53、C-erbB-2、VEGF表达的相关性研究[D].湖北：湖北中医学院,2008.
[35]刘起胜.乳腺癌中医辨证分型与GSTπ、P53表达的相关性分析[J].现代中西医结合杂志,2011,20(14)：1742-1743.
[36]刘永惠,郭少贤,常靖,等.丹参酮对血瘀证乳腺癌P53基因、mdm2基因表达的影响[J].陕西中医,2011,32(12)：1666-1667.
[37]崔同建,陈香莲,蒋云林,等.晚期大肠癌的病性证素与外周血P53、nm23的相关性研究[J].现代消化及介入诊疗,2011,16(4)：235-238.
[38]汪志霞.卵巢癌不同证型P-gp、P53的表达及亚砷酸、托泊替康等干预的体外研究[D].南京：南京中医药大学,2005.
[39]陈香莲.晚期大肠癌中医证素特点及其与血清肿瘤标志物及外周血P53、nm23的相关性研究[D].福州：福建中医药大学,2011.
[40]李净,胡建鹏,刘听,等.脑络欣通对脑缺血再灌注模型鼠神经细胞凋亡及P53蛋白表达的影响[J].安徽中医学院学报,2004,23(6)：20-22.
[41]陈建.血管内皮细胞hCASK-Id1通路对P53表达调控的机制研究[D].c重庆：第三军医大学,2007.
[1]Sha WC. Regulation of immune responses by NF kappa B/ Rel transcription factor [J]. Exp. Med.1998,187 (2):143-146.
[2]Wang D, Baldwin AS. Activation of nuclear factor-kappa B-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of ReIA/p65 on serine 529 [J]. Biol. Chem.1998,273 (45): 29411-29416.
[3]Haskill S, Beg AA, Tompkins SM, ex al. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell,1991,65(7):1281-1289.
[4]Thompson JE, Phillips RJ, Erdjument-Bromage H, ex al. IκBβ regulates the persistent response in a biphasic activation of NF-KB [J]. Cell,1995,80: 573-582.
[5]Whiteside ST, Israel A. I kappa B proteins:structure, function and regulation [J]. Semin. Cancer Biol.1997,8 (2):75-82.
[6]其其格.冠心病不稳定性心绞痛气虚血瘀证及炎症相关性研究[D].北京中医药大学：北京中医药大学,2010.
[7]常书福.冠状动脉微循环障碍的临床和实验研究[D].上海： 复旦大学,2010.
[8]顾大勇,曾祥元,马怖仁.NF-κB与微循环障碍[J].中国微循环,2001,5(1)：77-79.
[9]蒋素华.晚期缺血预适应对肾脏的保护作用及其机制研究[D].上海：复旦大学,2007.
[10]赵成广.内毒素诱导新生大鼠肾损害时肾组织NF-κB及TGF-β-1动态变化及其意义[D].沈阳：中国医科大学,2004.
[11]朱雅文.妊高征患者胎盘中NF-κB活化和母血TNF-α、ET及脐血TNF-α 含量变化的研究[D].郑州：郑州大学,2003.
[12]朱琳.危重病SIRS期患者中医证候研究及核因子-KB活化的临床意义[D].广州：广州中医药大学,2005.
[13]李永渝.核因子-κB作为急性胰腺炎治疗靶向的一些思考[A].第九届全国中西医结合普通外科学术交流大会暨胆道胰腺疾病新进展学习班论文汇编.[C].中国：杭州,2005：61-66.
[14]阚氏海,余崇林.NF-κB在重症急性胰腺炎肺损伤中的作用[J].泸州医学院学报,2007,30(4)：336-339.
[15]万涛.NF-κB、ICAM-1和炎症细胞因子在急性胰腺炎肝损伤中作用的实验研究[Z].国外医学临床生物化学与检验学分册,2005,26(12)：913-915.
[16]张喜平,金慧成,应荣超,等.黄芩甙对SAP大鼠多脏器细胞NF-κB表达的影响[Z].中国中西医结合外科杂志,2007,13(6)：550-554.
[17]Zhu, W., Q. Lv, et al. Protective Effect and Mechanism of Sodium Tanshinone ⅡA Sulfonate on Microcirculatory Disturbance of a-SM-actin Intestine in Rats with Sepsis [J]. Journal of Huazhong University of Science and Technology (Medical Sciences),2011,31 (4):441-445.
[18]刘雅,张海港,张翼冠,等.当归补血汤对气虚血瘀大鼠免疫功能及相关基因的调控[J].中药药理与临床,2009,25(5)：10-13.
[19]王玉德,崔勇,孙波.核因子-KB活化与重症急性胰腺炎微循环障碍的关系[J].中国交通医学杂志,2005,19(5)：431-432、435.
[20]郑健,吴群励,廖国华,等.益肾活血法治疗阿霉素肾病大鼠的实验研究[J].中国中西医结合杂志,2004,24(1)：124-128.
[21]张咏梅.室旁核内微量注射血管紧张素ⅡI对大鼠胃缺血—再灌注损伤的作用[D].杭州：浙江大学,2008.
[22]安尚玉.雌激素在缺氧／复氧心肌细胞中对NF-κB及粘附分子表达的影 响[D].长春：东北师范大学,2009.
[23]艾斯.益肾活血中药肾康灵干预小儿频复发性肾病与NF-κB、TXB-2、 6-keto-PGF-(1α)的临床研究[D].福州：福建中医学院,2008.
[24]郑健,吴群励,林青,等.肾康灵干预阿霉素肾病大鼠NF-κB的实验研究[J].福建中医学院学报,2005,15(2)：20-23.
[25]王升启,周喆,张红胜,等.复方丹参方治疗血瘀证的分子机理研究[A].中医药优秀论文选(下).[C].军事医学科学院放射与辐射医学研究所,2009：842-852.
[26]闫明先.氧化应激在胰腺纤维化中的作用及其分子机制的实验研究[D].济南：山东大学,2007.
[27]郑健,吴群励,林青,等.益肾活血中药肾康灵干预阿霉素肾病大鼠的药理研究[J].中国中西医结合肾病杂志,2004,5(10)：574-577.
[28]曾晓聪.替米沙坦对兔心肌缺血／再灌注损伤的影响[D].南宁：广西医科大学,2009.
[29]彭松林.参附注射液对肝脏缺血再灌注损伤中微循环障碍的影响[D].沈阳：中国医科大学,2005.
[30]王升启.复方丹参方治疗血瘀证的分子机理研究[Z].基础理论,国际先进,北京市：解放军军事医学科学院放射医学研究所,2005.12.30.
[31]郝旭亮.罗布麻总黄酮抗血栓作用物质基础及抗人脐静脉血管内皮细胞凋亡作用机理研究[D].太原：山西医科大学,2009.
[32]韩晶岩.内毒素引起的微循环障碍及中医药的改善作用[A].中国中西医结合学会微循环2009学术大会.[C].中国：浙江杭州,2009：4.
[33]黄政德,李鑫辉,张少泉,等.益气活血法对血瘀证兔缺血再灌注心肌细胞核因子κB蛋白表达影响[J].中华中医药学刊,2008,26(8)：1629-1631.
[34]张竞之,陈利国,胡小勤,等.黄芪多糖对原发性高血压病血瘀证患者Toll样受体4、核转录因子-KB表达的影响[J].中医杂志,2011,52(15)：1286-1289、1304.
[35]张竞之.黄芪多糖、丹皮酚对高血压病血瘀证内皮细胞损伤模型TLR4、 NF-κB表达的影响[D].广州：暨南大学,2009.
[36]陈敏.姜黄属中药及姜黄素活血化瘀抗动脉粥样硬化的文献整理及实验研究[D].北京：北京中医药大学,2011.
[37]韩笑,刘建勋,马晓斌,等.双参通冠方对急性心肌缺血再灌注NF-κB信号途径的影响[J].医学研究通讯,2004,33(11)：19-21.
[38]袁堂战,王卫星,陶绪雄,等.N-乙酰半胱氨酸联合维生素C对急性胰腺炎大鼠NF-κB和ICAM-1作用的实验研究[J].临床和实验医学杂志,2007,6(12)：17-19.
[39]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].沈阳：辽宁中医药大学,2007.
[40]李小波,李均,师晶丽.桃仁对单侧输尿管梗阻大鼠肾组织NF-kB、 TNF-α表达的影响[J].中国中医基础医学杂志,2006,12(7)：526-527.
[41]Baldwin AS Jr. The NF-kappa B and I kappa B proteins:new discoveries and insights [J]. Annu. Rev. Immunol.1996,14:649-683.
[42]Simeonidis S, Stauber D, Chen G, ex al. Mechanisms by which I kappa B proteins control NF-kappa B activity [J]. Proc. Natl. Acad. Sci. USA.1999, 96(1):49-54.
[43]May MJ, Ghosh S. Signal transduction through NF-kappa B [J]. Immunol. 1998,19 (2):80-88.
[44]Ohno H, Takimoto G, McKeithan TW. The candidate proto-oncogene Bcl-3 is related to genes implicated in cell lineage determination of cell cycle control [J]. Cell,1990,60:991-997.
[45]DiDonato JA, Hayakawa M, Rothwarf DM, ex al. A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B [J]. Nature,1997,388 (6642):548-554.
[1]Saha N, Moldovan F, Tardif G, et al. Interleukin-1 beta-converting enzyme/ Caspase-1 in human osteo-arthritic tissues:localization and role in the maturation of interleukin-1 beta and interleukin-18 [J]. Arthritis Rheum, 1999,42(8):1577-1587.
[2]Dinarello CA. Interleukin 1 and Interleukin 18 as mediators of inflammation and the aging process [J]. Am J Clin Nutr.2006,83(2):447-455.
[3]de Rivero JP, LotockiG, MarcilloAE, et al. A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury [J]. Neuroscience, 2008,28 (13):3404-3414.
[4]郭强,孔毅荣,付玲,等.炎性体的研究进展[J].军事医学科学院院刊,2007,31(5)：490-493。
[5]王萍.单核/巨噬细胞和vWF在慢性间质性肾炎肾组织上的表达及意义[D].中国医科大学：中国医科大学,2003.
[6]李建强.胆红素干预慢性阻塞性肺疾病和急性肺损伤的实验研究[Z].应用技术,国际先进,山西省：山西医科大学第二医院,2007.12.18.
[7]庞莹.ASC、caspase-1及IL-1p在牙周炎牙周组织中表达的动物实验研究[D].河北医科大学：河北医科大学,2010.
[8]Miural M, Zhu H, Nislow KH, et al. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death geneced-3 [J]. Cell,1993,75(4):653-660.
[9]Langford M P, McGee DJ, Ta KH, et al. Multiple Caspases mediate acute renal cell apoptosis induced by bacterial cell wall components [J]. RenFail, 2011,33(2):192-206.
[10]Chen P, Huang L, Zhang Y, et al. Anti-apoptotic effect of activated protein C on lipcpolysaccharide-slimulated human umbilical vein endothelial cells is associated with the inhibition of the Caspase-3 pathway [J]. MolMed Report,2010,3 (6):991-997.
[11]Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia [J]. Stroke,2009,40(5):331-339.
[12]沃兴德,丁志山.细胞凋亡与动脉粥样硬化[J].浙江中医学院学报,2001,25(2)：76-81.
[13]傅强,刘秉文.巨噬细胞、内皮细胞对高密度脂蛋白的氧化修饰[J].中国生物化学与分子生物学报,2001,17(5)：666-670.
[14]邱彦.Ox-LDL诱导单核／内皮细胞共培养系统VEGF上调及其促通透性升高的作用机制研究[D].第二军医大学：第二军医大学,2004.
[15]刘亮,刘旭盛,张晓启,等.巨噬细胞对血管内皮细胞增殖、Hoxb2、血管内皮生长因子受体和整合素αυβ3表达的影响[J].第一军医大学学报,2005,25(2)：148-151.
[16]刘亮.活化巨噬细胞对血管内皮细胞生物学特性及成血管作用的影响[D].第三军医大学：第三军医大学,2003.
[17]章必成,王俊,赵勇,等.替代性活化的巨噬细胞促进淋巴管内皮细胞增殖的机制[J].第四军医大学学报,2007,28(17)：1541-1543.
[18]章必成,王俊,赵勇,等.VEGF-C在替代性活化的巨噬细胞转分化为淋巴管内皮细胞中的作用[J].解放军医学杂志,2007,13(11)：1130-1133.
[19]章必成,王俊,赵勇,等.不同活化表型的巨噬细胞对淋巴管内皮细胞增殖、迁移和管样结构形成的影响[J].武汉大学学报(医学版),2007,28(3)：274-278.
[20]黄烨.冠心病血瘀证目标分子的鉴定、验证及功能分析[D].中国中医科学院：中国中医科学院,2011.
[21]徐拯.氢生理盐水对角叉菜胶诱导足肿胀的抗炎效应[D].第二军医大学：第二军医大学,2009.
[22]朱慧华,虞坚尔,张晓峰,等.平喘方对支气管哮喘模型小鼠巨噬细胞炎性蛋白-1α水平及CD86分子表达的实验研究[J].上海中医药杂志,2008,42(9)：58-62.
[23]赵志梅.补肾化瘀法治疗子宫内膜异位症不孕的研究[D].广州中医药大学：广州中医药大学,2000.
[24]黄朝义,朱兆荣,刘娟.桃红四物汤加减对母畜产后瘀血证疗效观察及药理初探[J].四川畜牧兽医学院学报,1994,8(4)：1-5.
[25]程青芳.防治泌乳期奶牛隐性乳房炎中草药的筛选及作用机理的研究[D].河北农业大学：河北农业大学,2002.
[1]Shepro D, M orel N M. Pericyte physiology [J]. FASEB,1993,7 (11):1031-1038.
[2]冯一梅,邹仲敏,徐辉.周细胞的研究进展[J].现代生物医学进展,2008,8(3)：571-589.
[3]王医术,李玉林,王心蕊,等.采用双重免疫组织化学及免疫电镜方法可将α-平滑肌肌动蛋白定位于乳腺癌间质新生血管周细胞[J].中国实验诊断学,2002,6(4)：203-205.
[4]王医术,李玉林,王心蕊,等.用a-SM-actin结合部位标记新生血管周细胞[J].吉林大学学报(医学版),2003,29(5)：594-598.
[5]程训民,江时森,马瑞,等.高血压合并糖尿病大鼠心肌毛细血管周细胞的观察[J].微循环学杂志,2008,18(1)：8-10.
[6]Patel, M. S., G. P. Taylor, et al. Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome." Am J Med Genet A, 2004,129A (3):294-299.
[7]Khourv J, Langeleben D. Platelet-activating factor stimulates lung pericyte growth in vitro. Am J Physiol,1996,270 (2):298-304.
[8]Khoury, J. and D. Langleben. Heparin-like molecules inhibit pulmonary vascular pericyte proliferation in vitro. Am J Physiol Lung Cell Mol Physiol,2000,279(2):L252-261.
[9]陈兰悦.AGE对DR周细胞的影响机制及银杏叶对DR的保护作用[D].长春：吉林大学,2004.
[10]倪劲松,王越晖,陈兰悦,等.银杏叶注射液对牛视网膜毛细血管周细胞的保护作用[J].吉林大学学报(医学版),2005,31(3)：368-371.
[11]Susan Olsona, Richard Oecklera, Xinmei Lia, et al. Angiotensin Ⅱ stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor. Am J Physaol Lung Cell Mol Physiol,2004,21:333-339.
[12]Klahr, S., and Morrissey, J. Angiotensin Ⅱ and gene expression m ladney. Am. J. Kidney Dis,1998,31:171-176.
[13]Marrero MB, Scheffer B, Paxton WC Heerdt L, et al. Direct stimulation of Jak/STAT pathway by the angiotensin Ⅱ AT1 receptor. Nature,1995,375: 247-250.
[14]Kodama Pan J, Makino S, Baba A, ex al. Angiotensin Ⅱ directly stimulates the JAK/STAT pathway through AT1 receptor in rat cardiomyocytes. Circulation,1996,94:401-405.
[15]Crawford DC, Chobanian AV, Brecher P. Angiotensin Ⅱ induces fibronechn expression associated with cardiac fibrosis in the rat. Circ Res.1994,74: 727-739.
[16]Sung CP, Arleth AJ, Storer BL, ex al. Angiotensin type 1 receptors mediate smooth muscle proliferation and endothelia biosynthesis in rat vascular smooth muscle [J]. Pharinacol Exp Then.1994,271:429-437.
[17]Imai T, Hirata Y, Emori T, ex al. Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells [J]. Hypertension,1992, 19:753-757.
[18]Arimura A, Asanuma F, Yagi H, ex al. Involvement of thromboxane A2 in bronchial hyperresponsiveness but not lung inflammation induced by bacterial lipopolysaccharide in guinea pigs. Eur J Pharmacol.1993,23: 13-21.
[19]Li P, Ferrario CM, Brosnihan KB. Losartan inhibits thromboxane A2-induced platelet aggregation and vascular constriction in spontaneously hypertensive rats. J Caxdtovasc Pharmacol.1998,198-205.
[20]Li P, Fukuhara M, Diz DI, ex al. Novel angiotensm Ⅱ AT (1) receptor antagonist irbesartan prevents thromboxane A (2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation. J Pharmacol Exp Ther.2000,292:238-246.
[21]李永荣,姚德厚,郭贵林,等.氟烷对慢性缺氧兔心肌p肾上腺素能受体的影响[J].中国应用生理学杂志,1996,12(1)：53-55.
[22]易岂建,钱永如,张远维.小儿慢性心力衰竭时血浆儿茶酚胺浓度及p-受体密度的改变[J].小儿急救医学杂志,1994,1(2)：76-78.
[23]冉光亮,仝识非,李永华,等.神经心源性晕厥患者血浆儿茶酚胺及红细胞膜p-受体的变化[J].临床心血管病杂志,2000,16(10)：457-458.
[24]尹智炜,史力生,陈志强,等.儿茶酚胺-p受体-cAMP系统在急性心肌梗死左室重塑中的生物学调控作用[J].中国老年学杂志,2006,26(4)：447-450.
[25]G.克劳斯.信号转导与调控的生物化学[M].北京：化学工业出版社,2005.
[26]Schutzer, W. E., H. Xue, et al. Effect of age on vascular beta2-adrenergic receptor desensitization is not mediated by the receptor coupling to Galphai proteins." J Gerontol A Biol Sci Med Sci,2006,61(9):899-906.
[27]Maeda, M., S. Kato, et al. Regulation of vascular smooth muscle proliferation and migration by beta2-chimaerin, a non-protein kinase C phorbol ester receptor. Int J Mol Med,2006,17(4):559-566.
[28]Dishy, V., G. G. Sofowora, et al. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med,2001,345(14):1030-1035.
[29]Eickelberg, O., M. Roth, et al. Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem, 1999,274(2):1005-1010.
[1]张静.中西医结合的微循环研究进展.微循环学杂志,2007,17(4)：1-7.
[2]Guo J, Sun K, Wang CS, et al. Protective effect s of dihydroxyl- phenyl lactic acid and salvianolic acid B on LPS- induced mesenter- ic microcirculatory disturbance in rat s. Shock,2008,29 (2):205-211.
[3]孙莉莎,吴航宇,徐江平,等.丹酚酸B对家兔血液流变性的影响.微循环学杂志,2003,13(1)：19-20.
[4]牛春雨,李继承,刘艳凯,等.夏至草醇提物对大鼠淋巴循环作用的实验研究.中国药学杂,2006,41(12)：914-917.
[5]张玉平,刘艳凯,姜华,等.夏至草生物碱对失血性休克大鼠淋巴微循环的影响.中国微循环,2006,10(3)：166-167.
[6]边永玲,刘正泉,牛春雨,等.夏至草醇提物对大鼠急性微循环障碍的影响.中国中西医结合急救杂志,2008,15(6)：338-341.
[7]于睿,兰宇.“以络论治”心肌微循环障碍.中华中医药学刊,2008,26(4)：828-829.
[8]陈士良,武效宏,王小冬.复方丹参注射液对缺血区冠脉循环的影响.中国医学研究与临床,2005,3(5)：13-1-16.
[9]赵娜,刘育英,卫晓红,等.复方丹参滴丸一次性预给药对缺血再灌注后大鼠心脏血流量和心肌损伤的改善作用.世界科学技术-中医药现代化,2008,10(3)：94-98.
[10]Xu XS, Ma ZZ, Wang F, et al. The Antioxidant cerebralcare granule (R) at tenuates cerebral microcirculatory disturbance during ischemia-reperfusion injury. Shock,2008,32 (2):201-209.
[11]徐想顺,王芳,刘育英,等.养血清脑颗粒对双侧颈动脉结扎-再通引起的蒙古沙鼠脑皮层微循环障碍和脑灌流量的改善作用.世界科学技术-中医药现代化,2008,10(3)：112-116.
[12]韩敏,薛茜,邹玉安,等.康脑液对脑缺血再灌注损伤大鼠软脑膜微循环的影响.中国微循环,2006,10(1)：22-25.
[13]韩敏,邹玉安,薛茜,等.康脑液对脑缺血再灌注损伤大鼠软脑膜微血流量的影响.中国临床康复,2006,10(23)：46-48.
[14]黄荣柏,黄效廷,胡锡琮,等.经门静脉灌注丹参对肝硬变患者门静脉血流动力学的影响.广西医学,2005,27(1)：98-99.
[15]Orie Y, Han J Y, Mori S, et al. Herbal cardiotonic pills prevent gut ischemia/ reperfusion- induced hepatic microvascular dysfunction in rats fed et hanol chronically. World J Gast roenterol,2005,11 (4):511-515.
[16]崔红燕,刘成,姜哲浩,等.扶正化瘀方对肝纤维化大鼠间质性基质金属蛋白酶活性的影响.上海中医药大学学报,2003,17(3)：35-38.
[17]谭春雨,谭善忠,蒋健,等.扶正化瘀方对肝纤维化大鼠肝脏明胶酶、TIMP-2和星状细胞凋亡的影响.上海中医药大学学报,2003,17(4)：40-44.
[18]Hen WX, Wang F, Liu YY, et al. Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gutischemia and reperfusion. World J Gast roenterol,2008,14 (1):29-37.
[19]刘学民,刘青光,潘承恩,等.白藜芦醇治疗重症急性胰腺炎肺微循环障碍的研究.中华普通外科杂志,2004,19(4)：253-1-254.
[20]赵桂峰,李竹庭,范英昌.丹酚酸B对缺氧再复氧心肌细胞内Ca2+浓度变化的影响.现代中西医结合杂志,2004,13(1)：19-20.
[21]宗刚军,陈景开,周辽军.银杏内酯B对体外培养乳鼠心肌细胞氧化损伤的保护作用.中国微循环,2004,8(4)：211-213.
[22]蒋丽敏,王雪峰,魏克伦,等.小柴胡汤对体外病毒性心肌炎模型的心肌细胞酶组织化学的影响.中华微生物学和免疫学杂志,2002,22(3)：298.
[23]郑世营,张晓膺,李虹,等.参附注射液对心肌细胞缺氧及缺氧／复氧Fas/ FasL表达的影响.中国急救医学,2005,25(12)：893-1-895.
[24]殷惠军,张颖,蒋路绒,等.西洋参叶总皂苷对急性心肌梗死大鼠心肌细胞凋亡及凋亡相关基因表达的影响.中国中西医结合杂志,2005,25(3)：232-235.
[25]王春玲,傅攀峰,李宏伟,等.葛根素对血管内皮细胞DNA损伤的保护作用.中国微循环,2004,8(6)：361-364.
[26]王怡,王少峡,姜志浩,等.首乌丹参方预处理对大鼠心肌缺血再灌注损伤iNOSmRNA表达的影响.辽宁中医杂志,2007,34(12)：1811-1814.
[27]王稳,徐标.丹参多酚酸盐对健康人血小板内皮型一氧化氮合酶活性的影响.中华高血压杂志,2007,15(7)：554-556.
[28]郑邦瑞,沈文律,文军,等.丹参注射液对重症急性胰腺炎大鼠胰腺NF-κB活化的影响.中国普外基础与临床杂志,2007,14(4)：392-395.
[29]刘建勋,韩笑,马晓斌,等.双参通冠方对急性心肌缺血再灌注模型核因子-KB信号途径及细胞间隙连接通讯的影响.中国中西医结合杂志,2005,25(3)：228-231.
[30]玉德,崔勇,孙波.核因子-κB活化与重症急性胰腺炎微循环障碍的关系.中国交通医学杂志,2005,19(5)：431-435.
[31]李石生,邓京振,赵守训,等.中药现代化研究的关键在于建立科学的现代中药理论体系——分子药性假说的提出[J].中国中西医结合杂志,2000,20(2)：83.
[32]欧阳兵,王振国,王鹏,等.“组群中药四性组合性效谱”假说及其论证[J].山东中医杂志,2006,25(3)：154.
[33]杨晓静,李和.桃仁油不皂化物与脂肪酸成分的分离与分析[J].农业与技术,2005,25(1)：84-86、90.
[34]杨晓静,李和.桃仁油不皂化物中甾醇和三萜醇的分离与鉴定[J].农业与技术,2005,25(2)：88-90、94.
[35]许惠玉,运晨霞,王雅贤.桃仁总蛋白对荷瘤鼠T淋巴细胞亚群及细胞凋亡的影响[J].齐齐哈尔医学院学报,2004,25(5)：485-487.
[36]潘会朝,秦文红.HPLC法测定苦杏仁和桃仁中苦杏仁甙的含量[J].世界最新医学信息文摘,2004,3(5)：1321-1322.