心绞痛贴膏穴位贴敷治疗冠心病的基础和临床研究
|
摘要
第一部分导师学术观点
目的：
探讨“心绞痛贴膏”穴位贴敷防治冠心病的中医理论依据。
方法：
总结整理导师“心绞痛贴膏”穴位贴敷治疗冠心病的中医理论。从“整体观念”的角度出发，分析经“皮部”治疗胸痹心痛的可行性；以“经络学说”中的“腧穴”和“经络”为切入点，分析穴位贴敷治疗胸痹心痛的药物作用路径。结合古代文献以及现代药理研究成果，证明导师“心绞痛贴膏”的组方依据和取穴依据。
结论：
中医理论支持“心绞痛贴膏”穴位贴敷治疗冠心病具有可行性和有效性。
第二部分心绞痛贴膏穴位贴敷预处理对大鼠急性心肌梗死的影响和作用机制目的：
探讨“心绞痛贴膏”穴位贴敷预处理对大鼠急性心肌梗死的干预效应及作用机制。
方法：
将健康Wistar大鼠55只随机分为正常组、模型组、对照组和治疗组，正常组10只，模型组、对照组和治疗组每组15只。在清洁级实验室以普通饲料饲养。对照组予硝酸甘油贴膜0.3mg心前区外贴，每次1贴，每日1次，每次维持24小时，疗程7天；治疗组予心绞痛贴膏（药物组成：川芎、丹参、冰片、乳香、没药、檀香、元胡等）穴位贴敷，每贴含生药量0.1g，每日一次，维持24h，双侧心俞、双侧足三里、神阙取穴，每穴1贴，疗程7天。第5天开始造模，对模型组、对照组和治疗组动物造成急性心肌梗死动物模型。具体方法是第5-7天每日贴敷后立即对模型组、对照组、治疗组动物注射异丙肾上腺素，采用多点皮下注射的方法，异丙肾上腺素用量为5mg/kg，第7天注射肾上腺素后，将各组存活动物用水合氯醛皮下注射麻醉（药量300mg/kg），麻醉成功后查心电图，以ST段明显上抬或下移为造模成功的初步判断标准，然后对各组动物腹主动脉采血、取心脏。光镜下观察心肌病理学形态，电镜下观察心肌超微结构；心电图测量ST段上抬或下移水平；全自动生化仪酶法检测肌酸激酶（Creatine kinase，CK）、肌酸激酶同工酶（Creatine kinase isoenzyme，CK-MB）、乳酸脱氢酶（LactateDehydrogenase，LDH）；免疫组化法测定丙二醛（Malondialdehyde，MDA）、过氧化物歧化酶（Superoxide Dismutase，SOD）、肿瘤坏死因子（Tumor Necrosis Factors TNF-α）、白介素-6（Interleukin，IL-6）、B细胞淋巴瘤/白血病-2B（cell-lymphoma/leukemia-2，Bcl-2）、Bax、半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）、P物质（Substance P，SP）、内皮细胞型一氧化氮合酶（endothelial nitric oxidesynthase，eNOS）、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、钙敏感受体(calcium—sensing receptor，CaSR)水平；荧光定量RT-PCR法测定eNOS、iNOS以及CaSR水平。
结果：
1光镜及电镜下观察：正常组心肌细胞呈正常表现。模型组心肌细胞坏死严重，可见心肌细胞核和心肌纤维排列紊乱、断裂及缺失，交织成网，横纹消失，心肌细胞核固缩，出现空白区，异染色质呈现团块状，相邻细胞闰盘间隙增宽。对照组和治疗组心肌细胞损伤坏死较模型组轻，但也可见少量断裂、缺损及空白区着色不均匀出现。透射电镜下：正常组心肌细胞无变化。模型组心肌线粒体损伤严重,双层膜结构不清，嵴断裂，大多数呈空泡状，部分溶解；细胞核染色质密集，部分胞浆溶解、消失，呈液化性坏死；肌原纤维极度松弛、出现空泡,部分肌丝断裂，闰盘局部性扩张，结构不清、溶解。对照组和治疗组线粒体损伤较轻，双层膜结构尚清晰，部分嵴断裂，细胞核结构基本完整，肌原纤维排列较整齐，可见肌丝断裂。
2心电图结果：模型组、对照组和治疗组ST段上抬或下移的绝对值较正常组明显高（P＜0.01）。对照组、治疗组ST段上抬或下移的绝对值均较模型组低，有统计学意义（P＜0.01），治疗组与对照组比较，无统计学意义。
3心肌酶学结果：模型组CK、CK-MB较正常组高（P＜0.01），对照组和治疗组CK水平较模型组低，与模型组比较，有统计学意义（P＜0.01）。对照组、治疗组CK-MB较模型组低，与模型组比较，有统计学意义（P＜0.05，P＜0.01）；治疗组CK、CK-MB水平与对照组比较，无统计学意义。各组LDH水平比较，均无统计学意义（P＞0.05）。
4免疫组化结果：
模型组MDA、TNF-α、IL-6、caspase3、Bax、SP较正常组高（P＜0.05），治疗组上述指标低于模型组（P＜0.05），治疗组TNF-α、Caspase-3、Bax、SP较对照组低（P＜0.05）；模型组SOD、bcl-2较正常组低，治疗组SOD、bcl-2较模型组和对照组高（P＜0.05）。
5eNOS、iNOS、CaSR免疫组化及荧光定量PCR结果
模型组、对照组、治疗组eNOS较正常组低（P＜0.05），对照组、治疗组eNOS较模型组高（P＜0.05），治疗组eNOS较对照组低（P＜0.05）。模型组、对照组、治疗组iNOS、CaSR较正常组高（P＜0.05），对照组、治疗组iNOS、CaSR较模型组低（P＜0.05），治疗组iNOS较对照组高（P＜0.05），治疗组CaSR较对照组低（P＜0.05）。
结论：
1心绞痛贴膏穴位贴敷预处理能够减轻AMI心肌损伤坏死程度，从病理学角度观察其作用效果与硝酸甘油贴膜外贴预处理效果相当，具体干预机制与以下4方面相关：通过抑制脂质过氧化、促进SOD生成、减少MDA；抑制TNF-α、IL-6具有抗炎作用；抑制CaSR减轻钙超载；上调eNOS的表达、下调iNOS的表达。
2心绞痛贴膏在调节NOS方面效果不及硝酸甘油贴膜，在抑制过氧化损伤、抗炎、抑制钙超载方面的效果优于硝酸甘油贴膜。
3心绞痛贴膏穴位贴敷预处理可能具有抑制AMI心肌细胞凋亡的作用，其机制与通过抑制casepase3促进bcl-2表达、抑制Bax的表达以及抑制CaSR有关。
4心绞痛贴膏具有镇痛作用，其机制可能与抑制P物质有关。
第三部分心绞痛贴膏穴位贴敷治疗气虚血瘀型冠心病不稳定性心绞痛的临床疗效观察
目的：
观察“心绞痛贴膏”治疗冠心病不稳定性心绞痛气虚血瘀型患者的临床疗效。
方法：
将60例气虚血瘀型冠心病不稳定性心绞痛患者随机分为治疗组和对照组。其中治疗组30例，对照组30例，对照组给予西医常规治疗，治疗组在西医常规治疗基础上给予“心绞痛贴膏”穴位贴敷，治疗10天。观察治疗前后的心绞痛发作次数、持续时间、程度和胸痛、胸闷、心悸、气短、乏力中医症状。
结果：
治疗组患者心绞痛症状、心绞痛积分、中医症状的有效率与对照组比较，有统计学意义（P＜0.05）。治疗组心绞痛发作次数、疼痛程度疗效均优于对照组（P=0.005P=0.006）；治疗组胸痛、气短、乏力疗效均优于对照组（P=0.028P=0.000P=0.010）。
结论：
在常规西药治疗基础上使用心绞痛贴膏，能够缓解气虚血瘀型不稳定性心绞痛患者的心绞痛，改善中医症状，特别是对心绞痛发作次数、疼痛程度、胸痛、气短、乏力有明显的缓解作用。
本研究的创新点在于总结了治疗冠心病的特色疗法，从基础研究和临床研究两方面验证了心绞痛贴膏穴位贴敷治疗冠心病的有效性，探索了一种用于减轻AMI程度的新方法，并研究了其作用机制。
PART I-Academic View of the Supervisor
Objective:
To discuss the TCM theoretical foundations of Professor Wang Fengrong’s“angina pectoris patch" acupoint stick application in the prevention andcontrol of coronary heart disease (CHD).
Methods:
The study summarizes the supervisor’s "angina pectoris patch" acupointapplication experience in the treatment of coronary heart disease and analyzesthe feasibility of chest obstruction heartache treatment through “skin” basedon “holistic concept”. It also analyzes the therapy path for acupointapplication on the treatment of chest obstruction heartache taking "acupuncturepoints" and "meridians" from meridian theory as the breakthrough point. The papermines the ancient literature of "Fifty-Two Diseases”,“Medical Origins" and"Theory of Parallel Prose” and traces the historical origins of acupointapplication therapy for coronary heart disease (CHD) and then combines classicalresults of the literature with modern pharmacological research to illustratethat the supervisor’s angina pectoris patch prescription basis and acupointsposition.
Conclusion:
With the foundational theories of TCM and meridian, the paper proves that the"angina pectoris patch" acupoint application can be used to treat coronary heartdisease (CHD). PART II–Discussion on "angina pectoris patch" acupoint applicationpretreatment on acute myocardial infarction rats and the influence of mechanism
Objectives:
To discuss the intervention effect of “angina pectoris patch” on acutemyocardial infarction and explore the intervention mechanism of “anginapectoris patch” on acute myocardial infarction from the perspectives of nitricoxide system adjustment and calcium sensitive receptor inhibition, which arebased on the observation of influence of “angina pectoris patch” acupointapplication pretreatment on acute myocardial infarction in the rat myocardialcell morphology, electrocardiogram and myocardial enzymology.
Methods:
55healthy wistar rats were randomly divided into normal group, model group,control group and treatment group, with10in normal group, and15in each ofthe model group, control group and treatment group. In clean grade laboratory,feeding with ordinary fodder for7days, the control group were given withNitroglycerin Plaster to0.3mg on the area before the heart, each time1stick,1times a day, keep24hours at a time, a total of seven days. Treatment groupwere given angina pectoris patch acupoint application, each patch0.1g, onceper day lasting for24hours, one patch per acupoint,1time per day and7daysin total. Medical modeling started on the4thday causing the model group, controlgroup and treatment group of animals to be acute myocardial infarction animalmodels with the specific method as follows. Between the5thday and the7thday,applying immediately after injection of animals in model group, control groupand treatment group isopropyl adrenaline, adopt the method of multi-pointsubcutaneous injection, isopropyl dosage of epinephrine is5mg/kg, afterepinephrine injection for7days, each live animals with chloral hydrateanesthesia subcutaneously dose (mg/kg), anesthesia after a successful checkelectrocardiogram (ecg), ST segment obvious up or down for building successfulpreliminary judgment standard, abdominal aorta to groups of animals blood, take heart. Lens under the observation of the myocardial pathology morphology andmyocardial ultrastructure were observed under electron microscope. Fullyautomatic biochemical instrument enzymatic detection of Creatine kinaseisoenzyme (CK-MB), Lactate Dehydrogenase (LDH). Immunohistochemical methodtest Malondialdehyde (MDA), Superoxide Dismutase (SOD), Tumor Necrosis factor(TNF-alpha), Interleukin-6(IL-6), B cell lymphoma/leukemia-2B (Bcl-2),Bax, cysteine, aspartic acid proteinase3(Caspase-3), Substance P (SP),endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase (iNOS)sensitive receptors, calcium (CaSR).Fluorescence quantitative PCR method typeeNOS, iNOS, CaSR.
Results:
Observed under optical microscope and electron microscope, myocardial cell ofnormal group shows normalshape. Model group myocyte necrosis, interwoven intoa network, horizontal stripes disappear, myocardial cell nucleus and visiblemuscle fibers arranged disorder, fault and loss, myocardial cell nucleuspycnosis, appear blank area, heterochromatin appears crumb, broadeningintercalated disc gap adjacent cells. Necrosis of myocardial cell damage in thecontrol group and treatment group compared with model group, but also a smallfracture and defect and uneven coloring appear blank area. Under the transmissionelectron microscopy (sem): normal group of myocardial cell no change. Myocardialmitochondrial injury model group, double membrane structure is not clear, crestfracture, most are vacuolated, partly dissolved; The nucleus chromatinconcentrated and part of the cytoplasm dissolved and disappeared, and showsliquefactive necrosis; Myofibril extremely flabby, vacuoles, some fracture,myofilament intercalated disc local expansion, structure is not clear, dissolved.Light in the control group and treatment group of mitochondrial damage and doublemembrane structure is clear, part of the crest fracture, the nucleus structurebasic integrity, myofibril arranged neatly, visible myofilament fracture. Model group, western medicine control group and Chinese medicine treatment groupthe absolute value of st-segment up or down significantly higher than normalgroup (P <0.01). Western medicine control group and traditional Chinese medicine(TCM) the absolute value of st-segment up or move down in treatment group werelower than model group, with statistical significance (P <0.01), Chinesemedicine treatment group compared with the western medicine control group,without statistical significance.
Control group and treatment group CK level was lower than those of model group,compared with model group, with statistical significance (P <0.01). CK-MBin the control group, treatment group was lower than those of model group,compared with model group, with statistical significance (P <0.05, P <0.01);Level of CK and CK-MB in treatment group compared with control group, withoutstatistical significance. Groups of LDH level comparison, there were nostatistical significance (P>0.05).
immunohistochemical results: model group MDA, TNF-α,IL-6, substance P,caspase3, Bax is high in the normal group (P <0.05). the treatment group TNF-α, substance P, caspase3, Bax was lower than those of control group (P <0.05).Model group, control group, treatment group, SOD, the BCL-2was lower thanthose of normal group, the SOD, the Bcl-2higher than the control group, treatmentgroup (P <0.05).
ENOS, iNOS，CaSR immunohistochemical results and fluorescent quantitative PCRresults: model group, control group, treatment group of iNOS higher than normalgroup,(P <0.05). The control group, treatment group of iNOS was lower thanthose of model group (P <0.05). INOS treatment group than the control group,2group, with statistical significance (P <0.05). Model group, control group,treatment group of eNOS was lower than those of normal group (P <0.05). ENOSin control group, treatment group compared with model group (P <0.05); ENOStreatment group was lower than those of control group, the comparison of two groups, there is statistical significance (P <0.05).model group, control groupand treatment group CaSR higher than normal group, with statistical significance(P <0.05). CaSR in control group, treatment group was lower than those of modelgroup (P <0.05); CaSR treatment group was lower than those of control group,the comparison of two groups, there is statistical significance (P <0.05).
Conclusion:
1angina patch of acupoint sticking pretreatment can reduce AMI necrosis ofmyocardial damage degree, its effect and the effect of nitroglycerin patchattached with pretreatment, the specific intervention mechanism related to thefollowing four aspects: by inhibiting lipid peroxidation, promoting SODgenerated, reduce the MDA; Suppress TNF alpha, IL-6, have anti-inflammatoryeffects; Inhibition of CaSR reduce calcium overload; Increase the expressionof eNOS, cut the expression of iNOS.
2angina pectoris patch in regulating NOS aspects effect is not good asNitroglycerin Plaster, in inhibiting peroxidation damage, anti-inflammatory,inhibiting calcium overload effect superior to Nitroglycerin Plaster.3angina pectoris patch acupoint pretreatment may inhibit myocardial cellapoptosis after AMI. The mechanism is inhibited casepase3, promoting bcl-2expression and inhibit the expression of Bax and inhibition of CaSR.4anginapectoris patch has analgesic action, its mechanism may be related to inhibitingsubstance P.
PART III-Clinical Curative Effect Observation of "angina pectoris patch"acupoint application therapy in treatment of both Qi deficiency and blood stasissyndrome of coronary heart disease (CHD) unstable angina pectoris
Objective:
To observe the clinical treatment effect of “angina pectoris patch” on coronaryheart disease (CHD) unstable angina patients with Qi deficiency and blood stasis.
Methods:
60patients of Qi deficiency and blood stasis syndrome of coronary heart diseaseunstable angina patients, according to random number table method, were randomlydivided into treatment group and control group, with30patients in each group.Control group were given conventional western medicine treatment and thetreatment group, were given "angina pectoris patch" acupoint applicationtreatment for10days, on the basis of the conventional western medicinetreatment. Angina pectoris attack frequency, duration, numbers of pains and TCMsymptoms such as chest pain, chest tightness, palpitations, shortness of breath,fatigue, constipation.
Results:
Angina pectoris symptoms, Chinese medicine treatment group effective comparedwith control group, was statistical significant (P <0.05). Attack frequencyof angina pectoris, pain degree of curative effect of treatment group weresuperior to control group (P=0.005, P=0.006); Chest pain, shortness of breath,fatigue effect of treatment group were superior to control group (P=0.028,P=0.000, P=0.010).
Conclusion:
On the basis of conventional western medicine treatment, angina pectoris patch,can ease the qi deficiency blood stasis type of angina, unstable angina patientsimprove TCM symptoms, especially to attack frequency of angina pectoris, andthe degree of pain, chest pain, shortness of breath, fatigue has obvious effect.
目的：
探讨“心绞痛贴膏”穴位贴敷防治冠心病的中医理论依据。
方法：
总结整理导师“心绞痛贴膏”穴位贴敷治疗冠心病的中医理论。从“整体观念”的角度出发，分析经“皮部”治疗胸痹心痛的可行性；以“经络学说”中的“腧穴”和“经络”为切入点，分析穴位贴敷治疗胸痹心痛的药物作用路径。结合古代文献以及现代药理研究成果，证明导师“心绞痛贴膏”的组方依据和取穴依据。
结论：
中医理论支持“心绞痛贴膏”穴位贴敷治疗冠心病具有可行性和有效性。
第二部分心绞痛贴膏穴位贴敷预处理对大鼠急性心肌梗死的影响和作用机制目的：
探讨“心绞痛贴膏”穴位贴敷预处理对大鼠急性心肌梗死的干预效应及作用机制。
方法：
将健康Wistar大鼠55只随机分为正常组、模型组、对照组和治疗组，正常组10只，模型组、对照组和治疗组每组15只。在清洁级实验室以普通饲料饲养。对照组予硝酸甘油贴膜0.3mg心前区外贴，每次1贴，每日1次，每次维持24小时，疗程7天；治疗组予心绞痛贴膏（药物组成：川芎、丹参、冰片、乳香、没药、檀香、元胡等）穴位贴敷，每贴含生药量0.1g，每日一次，维持24h，双侧心俞、双侧足三里、神阙取穴，每穴1贴，疗程7天。第5天开始造模，对模型组、对照组和治疗组动物造成急性心肌梗死动物模型。具体方法是第5-7天每日贴敷后立即对模型组、对照组、治疗组动物注射异丙肾上腺素，采用多点皮下注射的方法，异丙肾上腺素用量为5mg/kg，第7天注射肾上腺素后，将各组存活动物用水合氯醛皮下注射麻醉（药量300mg/kg），麻醉成功后查心电图，以ST段明显上抬或下移为造模成功的初步判断标准，然后对各组动物腹主动脉采血、取心脏。光镜下观察心肌病理学形态，电镜下观察心肌超微结构；心电图测量ST段上抬或下移水平；全自动生化仪酶法检测肌酸激酶（Creatine kinase，CK）、肌酸激酶同工酶（Creatine kinase isoenzyme，CK-MB）、乳酸脱氢酶（LactateDehydrogenase，LDH）；免疫组化法测定丙二醛（Malondialdehyde，MDA）、过氧化物歧化酶（Superoxide Dismutase，SOD）、肿瘤坏死因子（Tumor Necrosis Factors TNF-α）、白介素-6（Interleukin，IL-6）、B细胞淋巴瘤/白血病-2B（cell-lymphoma/leukemia-2，Bcl-2）、Bax、半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）、P物质（Substance P，SP）、内皮细胞型一氧化氮合酶（endothelial nitric oxidesynthase，eNOS）、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、钙敏感受体(calcium—sensing receptor，CaSR)水平；荧光定量RT-PCR法测定eNOS、iNOS以及CaSR水平。
结果：
1光镜及电镜下观察：正常组心肌细胞呈正常表现。模型组心肌细胞坏死严重，可见心肌细胞核和心肌纤维排列紊乱、断裂及缺失，交织成网，横纹消失，心肌细胞核固缩，出现空白区，异染色质呈现团块状，相邻细胞闰盘间隙增宽。对照组和治疗组心肌细胞损伤坏死较模型组轻，但也可见少量断裂、缺损及空白区着色不均匀出现。透射电镜下：正常组心肌细胞无变化。模型组心肌线粒体损伤严重,双层膜结构不清，嵴断裂，大多数呈空泡状，部分溶解；细胞核染色质密集，部分胞浆溶解、消失，呈液化性坏死；肌原纤维极度松弛、出现空泡,部分肌丝断裂，闰盘局部性扩张，结构不清、溶解。对照组和治疗组线粒体损伤较轻，双层膜结构尚清晰，部分嵴断裂，细胞核结构基本完整，肌原纤维排列较整齐，可见肌丝断裂。
2心电图结果：模型组、对照组和治疗组ST段上抬或下移的绝对值较正常组明显高（P＜0.01）。对照组、治疗组ST段上抬或下移的绝对值均较模型组低，有统计学意义（P＜0.01），治疗组与对照组比较，无统计学意义。
3心肌酶学结果：模型组CK、CK-MB较正常组高（P＜0.01），对照组和治疗组CK水平较模型组低，与模型组比较，有统计学意义（P＜0.01）。对照组、治疗组CK-MB较模型组低，与模型组比较，有统计学意义（P＜0.05，P＜0.01）；治疗组CK、CK-MB水平与对照组比较，无统计学意义。各组LDH水平比较，均无统计学意义（P＞0.05）。
4免疫组化结果：
模型组MDA、TNF-α、IL-6、caspase3、Bax、SP较正常组高（P＜0.05），治疗组上述指标低于模型组（P＜0.05），治疗组TNF-α、Caspase-3、Bax、SP较对照组低（P＜0.05）；模型组SOD、bcl-2较正常组低，治疗组SOD、bcl-2较模型组和对照组高（P＜0.05）。
5eNOS、iNOS、CaSR免疫组化及荧光定量PCR结果
模型组、对照组、治疗组eNOS较正常组低（P＜0.05），对照组、治疗组eNOS较模型组高（P＜0.05），治疗组eNOS较对照组低（P＜0.05）。模型组、对照组、治疗组iNOS、CaSR较正常组高（P＜0.05），对照组、治疗组iNOS、CaSR较模型组低（P＜0.05），治疗组iNOS较对照组高（P＜0.05），治疗组CaSR较对照组低（P＜0.05）。
结论：
1心绞痛贴膏穴位贴敷预处理能够减轻AMI心肌损伤坏死程度，从病理学角度观察其作用效果与硝酸甘油贴膜外贴预处理效果相当，具体干预机制与以下4方面相关：通过抑制脂质过氧化、促进SOD生成、减少MDA；抑制TNF-α、IL-6具有抗炎作用；抑制CaSR减轻钙超载；上调eNOS的表达、下调iNOS的表达。
2心绞痛贴膏在调节NOS方面效果不及硝酸甘油贴膜，在抑制过氧化损伤、抗炎、抑制钙超载方面的效果优于硝酸甘油贴膜。
3心绞痛贴膏穴位贴敷预处理可能具有抑制AMI心肌细胞凋亡的作用，其机制与通过抑制casepase3促进bcl-2表达、抑制Bax的表达以及抑制CaSR有关。
4心绞痛贴膏具有镇痛作用，其机制可能与抑制P物质有关。
第三部分心绞痛贴膏穴位贴敷治疗气虚血瘀型冠心病不稳定性心绞痛的临床疗效观察
目的：
观察“心绞痛贴膏”治疗冠心病不稳定性心绞痛气虚血瘀型患者的临床疗效。
方法：
将60例气虚血瘀型冠心病不稳定性心绞痛患者随机分为治疗组和对照组。其中治疗组30例，对照组30例，对照组给予西医常规治疗，治疗组在西医常规治疗基础上给予“心绞痛贴膏”穴位贴敷，治疗10天。观察治疗前后的心绞痛发作次数、持续时间、程度和胸痛、胸闷、心悸、气短、乏力中医症状。
结果：
治疗组患者心绞痛症状、心绞痛积分、中医症状的有效率与对照组比较，有统计学意义（P＜0.05）。治疗组心绞痛发作次数、疼痛程度疗效均优于对照组（P=0.005P=0.006）；治疗组胸痛、气短、乏力疗效均优于对照组（P=0.028P=0.000P=0.010）。
结论：
在常规西药治疗基础上使用心绞痛贴膏，能够缓解气虚血瘀型不稳定性心绞痛患者的心绞痛，改善中医症状，特别是对心绞痛发作次数、疼痛程度、胸痛、气短、乏力有明显的缓解作用。
本研究的创新点在于总结了治疗冠心病的特色疗法，从基础研究和临床研究两方面验证了心绞痛贴膏穴位贴敷治疗冠心病的有效性，探索了一种用于减轻AMI程度的新方法，并研究了其作用机制。
PART I-Academic View of the Supervisor
Objective:
To discuss the TCM theoretical foundations of Professor Wang Fengrong’s“angina pectoris patch" acupoint stick application in the prevention andcontrol of coronary heart disease (CHD).
Methods:
The study summarizes the supervisor’s "angina pectoris patch" acupointapplication experience in the treatment of coronary heart disease and analyzesthe feasibility of chest obstruction heartache treatment through “skin” basedon “holistic concept”. It also analyzes the therapy path for acupointapplication on the treatment of chest obstruction heartache taking "acupuncturepoints" and "meridians" from meridian theory as the breakthrough point. The papermines the ancient literature of "Fifty-Two Diseases”,“Medical Origins" and"Theory of Parallel Prose” and traces the historical origins of acupointapplication therapy for coronary heart disease (CHD) and then combines classicalresults of the literature with modern pharmacological research to illustratethat the supervisor’s angina pectoris patch prescription basis and acupointsposition.
Conclusion:
With the foundational theories of TCM and meridian, the paper proves that the"angina pectoris patch" acupoint application can be used to treat coronary heartdisease (CHD). PART II–Discussion on "angina pectoris patch" acupoint applicationpretreatment on acute myocardial infarction rats and the influence of mechanism
Objectives:
To discuss the intervention effect of “angina pectoris patch” on acutemyocardial infarction and explore the intervention mechanism of “anginapectoris patch” on acute myocardial infarction from the perspectives of nitricoxide system adjustment and calcium sensitive receptor inhibition, which arebased on the observation of influence of “angina pectoris patch” acupointapplication pretreatment on acute myocardial infarction in the rat myocardialcell morphology, electrocardiogram and myocardial enzymology.
Methods:
55healthy wistar rats were randomly divided into normal group, model group,control group and treatment group, with10in normal group, and15in each ofthe model group, control group and treatment group. In clean grade laboratory,feeding with ordinary fodder for7days, the control group were given withNitroglycerin Plaster to0.3mg on the area before the heart, each time1stick,1times a day, keep24hours at a time, a total of seven days. Treatment groupwere given angina pectoris patch acupoint application, each patch0.1g, onceper day lasting for24hours, one patch per acupoint,1time per day and7daysin total. Medical modeling started on the4thday causing the model group, controlgroup and treatment group of animals to be acute myocardial infarction animalmodels with the specific method as follows. Between the5thday and the7thday,applying immediately after injection of animals in model group, control groupand treatment group isopropyl adrenaline, adopt the method of multi-pointsubcutaneous injection, isopropyl dosage of epinephrine is5mg/kg, afterepinephrine injection for7days, each live animals with chloral hydrateanesthesia subcutaneously dose (mg/kg), anesthesia after a successful checkelectrocardiogram (ecg), ST segment obvious up or down for building successfulpreliminary judgment standard, abdominal aorta to groups of animals blood, take heart. Lens under the observation of the myocardial pathology morphology andmyocardial ultrastructure were observed under electron microscope. Fullyautomatic biochemical instrument enzymatic detection of Creatine kinaseisoenzyme (CK-MB), Lactate Dehydrogenase (LDH). Immunohistochemical methodtest Malondialdehyde (MDA), Superoxide Dismutase (SOD), Tumor Necrosis factor(TNF-alpha), Interleukin-6(IL-6), B cell lymphoma/leukemia-2B (Bcl-2),Bax, cysteine, aspartic acid proteinase3(Caspase-3), Substance P (SP),endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase (iNOS)sensitive receptors, calcium (CaSR).Fluorescence quantitative PCR method typeeNOS, iNOS, CaSR.
Results:
Observed under optical microscope and electron microscope, myocardial cell ofnormal group shows normalshape. Model group myocyte necrosis, interwoven intoa network, horizontal stripes disappear, myocardial cell nucleus and visiblemuscle fibers arranged disorder, fault and loss, myocardial cell nucleuspycnosis, appear blank area, heterochromatin appears crumb, broadeningintercalated disc gap adjacent cells. Necrosis of myocardial cell damage in thecontrol group and treatment group compared with model group, but also a smallfracture and defect and uneven coloring appear blank area. Under the transmissionelectron microscopy (sem): normal group of myocardial cell no change. Myocardialmitochondrial injury model group, double membrane structure is not clear, crestfracture, most are vacuolated, partly dissolved; The nucleus chromatinconcentrated and part of the cytoplasm dissolved and disappeared, and showsliquefactive necrosis; Myofibril extremely flabby, vacuoles, some fracture,myofilament intercalated disc local expansion, structure is not clear, dissolved.Light in the control group and treatment group of mitochondrial damage and doublemembrane structure is clear, part of the crest fracture, the nucleus structurebasic integrity, myofibril arranged neatly, visible myofilament fracture. Model group, western medicine control group and Chinese medicine treatment groupthe absolute value of st-segment up or down significantly higher than normalgroup (P <0.01). Western medicine control group and traditional Chinese medicine(TCM) the absolute value of st-segment up or move down in treatment group werelower than model group, with statistical significance (P <0.01), Chinesemedicine treatment group compared with the western medicine control group,without statistical significance.
Control group and treatment group CK level was lower than those of model group,compared with model group, with statistical significance (P <0.01). CK-MBin the control group, treatment group was lower than those of model group,compared with model group, with statistical significance (P <0.05, P <0.01);Level of CK and CK-MB in treatment group compared with control group, withoutstatistical significance. Groups of LDH level comparison, there were nostatistical significance (P>0.05).
immunohistochemical results: model group MDA, TNF-α,IL-6, substance P,caspase3, Bax is high in the normal group (P <0.05). the treatment group TNF-α, substance P, caspase3, Bax was lower than those of control group (P <0.05).Model group, control group, treatment group, SOD, the BCL-2was lower thanthose of normal group, the SOD, the Bcl-2higher than the control group, treatmentgroup (P <0.05).
ENOS, iNOS，CaSR immunohistochemical results and fluorescent quantitative PCRresults: model group, control group, treatment group of iNOS higher than normalgroup,(P <0.05). The control group, treatment group of iNOS was lower thanthose of model group (P <0.05). INOS treatment group than the control group,2group, with statistical significance (P <0.05). Model group, control group,treatment group of eNOS was lower than those of normal group (P <0.05). ENOSin control group, treatment group compared with model group (P <0.05); ENOStreatment group was lower than those of control group, the comparison of two groups, there is statistical significance (P <0.05).model group, control groupand treatment group CaSR higher than normal group, with statistical significance(P <0.05). CaSR in control group, treatment group was lower than those of modelgroup (P <0.05); CaSR treatment group was lower than those of control group,the comparison of two groups, there is statistical significance (P <0.05).
Conclusion:
1angina patch of acupoint sticking pretreatment can reduce AMI necrosis ofmyocardial damage degree, its effect and the effect of nitroglycerin patchattached with pretreatment, the specific intervention mechanism related to thefollowing four aspects: by inhibiting lipid peroxidation, promoting SODgenerated, reduce the MDA; Suppress TNF alpha, IL-6, have anti-inflammatoryeffects; Inhibition of CaSR reduce calcium overload; Increase the expressionof eNOS, cut the expression of iNOS.
2angina pectoris patch in regulating NOS aspects effect is not good asNitroglycerin Plaster, in inhibiting peroxidation damage, anti-inflammatory,inhibiting calcium overload effect superior to Nitroglycerin Plaster.3angina pectoris patch acupoint pretreatment may inhibit myocardial cellapoptosis after AMI. The mechanism is inhibited casepase3, promoting bcl-2expression and inhibit the expression of Bax and inhibition of CaSR.4anginapectoris patch has analgesic action, its mechanism may be related to inhibitingsubstance P.
PART III-Clinical Curative Effect Observation of "angina pectoris patch"acupoint application therapy in treatment of both Qi deficiency and blood stasissyndrome of coronary heart disease (CHD) unstable angina pectoris
Objective:
To observe the clinical treatment effect of “angina pectoris patch” on coronaryheart disease (CHD) unstable angina patients with Qi deficiency and blood stasis.
Methods:
60patients of Qi deficiency and blood stasis syndrome of coronary heart diseaseunstable angina patients, according to random number table method, were randomlydivided into treatment group and control group, with30patients in each group.Control group were given conventional western medicine treatment and thetreatment group, were given "angina pectoris patch" acupoint applicationtreatment for10days, on the basis of the conventional western medicinetreatment. Angina pectoris attack frequency, duration, numbers of pains and TCMsymptoms such as chest pain, chest tightness, palpitations, shortness of breath,fatigue, constipation.
Results:
Angina pectoris symptoms, Chinese medicine treatment group effective comparedwith control group, was statistical significant (P <0.05). Attack frequencyof angina pectoris, pain degree of curative effect of treatment group weresuperior to control group (P=0.005, P=0.006); Chest pain, shortness of breath,fatigue effect of treatment group were superior to control group (P=0.028,P=0.000, P=0.010).
Conclusion:
On the basis of conventional western medicine treatment, angina pectoris patch,can ease the qi deficiency blood stasis type of angina, unstable angina patientsimprove TCM symptoms, especially to attack frequency of angina pectoris, andthe degree of pain, chest pain, shortness of breath, fatigue has obvious effect.
引文
[1]赵明地.心绞痛贴膏治疗冠心病心绞痛(气虚血瘀型)的临床疗效观察.辽宁中医药大学.2010.
[2]陈维.心绞痛贴膏外治冠心病稳定性心绞痛(痰浊痹阻证)的临床疗效观察.辽宁中医药大学.2010.
[3]清·吴尚先,理论骈文,北京,中国中医药出版社,1995年:50.
[4]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001,23(12):864-867.
[5]赵明地,王凤荣.穴位贴敷治疗冠心病心绞痛理论基础探要[J].实用中医内科杂志,2010,24(4):33-34.
[6]殷建明,罗陆一,张大创等.通心贴穴位外治冠心病心绞痛临床研究[J].中西医结合心脑血管病杂志,2009,7(10):1138-1140.
[7]韩亚男.中药穴位敷贴对心肌缺血大鼠心肌酶的影响[J].上海中医药大学学报,2001,15(3):58-59.
[8]刘新国,周莉玲,郭丽蓉等.环维黄杨星D透皮贴剂抗心肌缺血作用的研究[J].时珍国医国药,2010,21(11):2723-2725.
[9]张颖,孙操.冠心舒贴的抗心肌缺血的实验研究[J].黑龙江医药,2007,20(3):230-231.
[10]李建宇,李怡,龚海英等.蕨麻正丁醇提取部位对小鼠急性心肌缺血损伤的保护作用[J].中西医结合学报,2009,7(1):48-52.
[11]修颖.冠心膏内服配合冠心贴贴敷治疗冠心病稳定型劳累性心绞痛的临床观察[J].河北中医,2010,32(7):981-983.
[12]姜明华.冠心药膜治疗冠心病稳定性心绞痛临床观察[J].中医药学刊,2006,24(10):1959-1960.
[13]柏业军.张培影运用通络保心贴治疗不稳定性心绞痛的经验[J].中医药临床杂志,2010,22(7):617-618.
[14]李根,陈鹏毅,邢洁等.护心贴外敷心俞内关穴治疗冠心病心绞痛临床观察[J].山西中医,2008,24(10):27-28.
[15]华浩明,王家骜,姚祖培等.宁心膏透皮给药治疗冠心病心绞痛50例临床研究[J].中医杂志,2004,45(11):834-835,851.
[16]江武.通痹散穴位贴敷治疗冠心病50例临床观察[J].光明中医,2007,22(12):80-81.
[17]吴泽铭,邢洁,张大创等.通心贴外敷心俞穴对冠心病心绞痛NO、NOS、SOD、MDA的影响[J].河南中医学院学报,2007,22(4):35-36.
[18]邢洁.通心贴外敷心俞与内关穴治疗冠心病心绞痛临床观察[J].山西中医,2007,23(4):62-63.
[19]冯润芬,罗陆一.通心贴心俞穴外敷治疗冠心病心绞痛60例临床观察[J].中国中医药科技,2005,12(1):47-48.
[20]殷建明,罗陆一,张大创等.通心贴穴位外治冠心病心绞痛临床研究[J].中西医结合心脑血管病杂志,2009,7(10):1138-1140.
[21]罗陆一,冯润芬,吴泽民等.温肾化痰活血法心腧穴位外治治疗冠心病心绞痛观察[J].中医药学刊,2006年,24(6):984-985.
[22]宋丽君.心痛散内服外用治疗缺血型冠心病心绞痛120例[J].中国中医药信息杂志,2002,9(11):42.
[23]周建中.克心痛药膜穴位贴敷治疗冠心病心绞痛临床疗效观察[J].江苏临床医学杂志,2002,6(6):599.
[24]高云,高晓光.通心膏贴敷穴位治疗冠心病心绞痛61例疗效观察[J].山西中医学院学报,2007,8(4):25-26.
[25]姜爱平,谢任禹,栗欣等.中药穴位敷贴治疗冠心病心绞痛临床观察[J].中国中医药信息杂志,2003,10(1):41-42.
[26]张俊.自制保心膏治疗冠心病心绞痛48例临床观察[J].中西医结合心脑血管病杂志,2003,1(4):231.
[27]李洪韬.中药贴敷配合外洗治疗冠心病合并高血压病45例[J].中医外治杂志,2008,17(4):13.
[28]Chen YF,Kobayashi S,Chen J,et al.Short term triiodo-L-thyroninetreatment inhibits cardiac myocyte apoptosis in border area aftermyocardial infarction in rats [J].J Mol Cell Cardiol,2008,44(1):180-187.
[29]Gu X,Cheng L,Chueng W L, et al. Neovascularization of IschemicMyocardium by Newly Isolated Tannins Prevents Cardiomyocyte Apoptosis andImproves Cardiac Function[J]. MolMed,2006；12(11-12):275-283.
[30]姚玉宇,马根山,刘乃丰,等.急性心肌梗死后凋亡和炎症及相关因子的动态变化[J].江苏医药,2008,34(12):1271-1273.
[31]王学颖,王阶,杨戈,等.血塞通软胶囊对心肌梗死大鼠血流动力学及心肌细胞凋亡的影响[J].中西医结合学报,2010,8(3):269-274.
[32]王学颖,杨戈,王阶,等.溶血磷脂酸及其受体在急性心肌梗死早期大鼠心肌细胞凋亡调控中的作用及活血方药干预的研究[J].中华中医药杂志,2010,25(12):1999-2002
[33]郭艳,殷惠军,史大卓,等.心脑舒通胶囊对高脂血症大鼠心肌梗死后心肌细胞凋亡及Bax、 Bcl-2蛋白表达的影响[J].中国中西医结合杂志,2006,26(6):541-544.
[34]陈跃峰,杨跃进,阮英茆,等.大鼠急性心肌梗死后心肌细胞凋亡和半胱天冬蛋白酶-3的表达及卡维地洛的防治作用[J].中国循环杂志2004,19(6):454-458.
[35]肖骏,马渝,邓松柏,等.芪苈强心对心肌梗死后犬鼠心肌细胞凋亡的影响[J].中国病理生理杂志,2012,28(6):1045-1050.
[36]Sinagra G,Bussani R,Abbate A, et al.Left ventricular diastolic fillingpattern at Doppler echocardiography and apoptotic rate in fatal acutemyocardial infarction [J].American Journal of Cardiology,2007；99(3):307–309．
[37] Olivetti G,Quaini F,Sala R,et al．Acute myocardial infarction inhumans is associated with activation of programmed myocyte cell death inthe surviving portion of the heart．Mol Cell Cardiol,1996；28(9):2005–2016．
[38]James T N． The variable morphological coexistence of apoptosis andnecrosis in human myocardial infarction: significance for understandingits pathogenesis, clinical course, diagnosis and prognosis． CoronaryArtery Disease,1998；9(5):291–308．
[39]Bardales RH, Hailey LS, Xie SS,et al．In situ apoptosis assay for thedetection of early acute myocardial infarction [J].American Journal ofPathology,1996；149(3):821–829．
[40]Ogino A,Takemura G, Kanamori H.Amlodipine inhibits granulation tissuecell apoptosis through reducing calcineurin activity to attenuatepostinfarction cardiac remodeling: Am-J-Physiol-Heart-Circ-Physiol.2007Oct;293(4): H2271-80.
[41]陈跃峰,杨跃进,陈曦.β受体阻滞剂阿替洛尔和酒石酸美托洛尔对大鼠急性心肌梗死后心肌细胞凋亡及凋亡相关基因表达的作用[J].中国医学科学院学报2006,28(4)538-543.
[42]Feng QZ,Wei LX,Yi J,et al.Relationship between the expression ofFas,bcl-2and apoptosis of cardiomyccytes in experimental myocardialischemia in rats[J].Zonghua Bing Li Xue Za Zhi,2004,33(2):151-154.vonHarsdorf R.Fas-ten your seat belt:anti-apoptotic treatment in heartfailure takes off[J].Circ Rec,2003,95(6):554-556.
[43]Contini P,GhioM,Merlo A,et al.Apoptosis of antigen-specific Tlymphocytes upon the engagement of CD8by soluble HLA calss I moleculesif Fas ligand/Fas mediated:evidence for the involvement of p56lck,calciumcalmodulin kinase II,and Calcium-independent protein kinase C signalingpathways and for NF-kappaB and NF-AT nuclear traslocation[J].JImmunol,2005,175(11):7244-7254.
[44]麦炜颐,马莉,黄裕立,等.ACE抑制剂Ramipril对大鼠急性心肌梗死后心肌细胞凋亡和左室重构的影响[J].中山大学学报(医学科学版),2008,29(5):550-555.
[45]Huang YL,Kuang J,Hu YZ,et al. Bone marrow stromal cell transplantationcombined with angiotensin-converting enzyme inhibitor treatment in ratwith acute myocardial infarction and the role of insulin-like growthfactor-1. Cytotherapy.2012May;14(5):563-9.
[46]Maack C, Kartes T, Kilter H.Oxygen free radical release in human failingmyocardium is associated with increased activity of rac1-GTPase andrepresents a target for statin treatment.
[47]叶强,陈良海,刘应才.辛伐他汀通过Akt/GSK3β通路抑制心肌梗死后心肌细胞凋亡[J].中国药理学通报,2011,27(12):1656-1660.
[48]HM,M llmann H,Hilpert P,et al.Activated cell survivalcascade protectscardiomyocytes from cell death in Tako-Tsubo cardiomyopathy［J］.Eur J HeartFail,2009,11(8):758-64．
[49]Muslin AJ.Akt2:A critical regulator of cardiomyocyte survival andmetabolism［J］.Pedi Card,2011(32):317-22．
[50]DeBosch B,Sambandam N,Weinheimer C,et al.Akt2regulates cardiacmetablism and cardiomyocyte survival ［J］.J Biol Chem,2006,281(43):32841-51．
[51]许香梅,任晓敏,刘曙光.醛固酮受体拮抗剂对急性心肌梗死大鼠心肌细胞凋亡的影响临床荟萃2012,27(14):1230-1233.
[52]叶周恒,杨玉鹤,许骥,等.醛固酮诱导心室重构作用及机制[J].心肺血管病杂志,2011,30(2):174-176.
[53]Hayashi H,Kobara M,Abe M.Aldosterone nongenomically produces NADPHoxidase-dependent reactive oxygen species and induces myocyte apoptosis.Hypertens Res,200831(2):363-75.
[54]夏勇,张勇,李东野,等.塞来昔布对心肌梗死后心肌细胞凋亡的影响中国病理生理杂志,2007,23(1):49-52.
[55]张勇,夏勇,李东野.硝酸异山梨酯对心肌梗死后心肌细胞凋亡的影响[J].中华心血管病杂志,2004,32(2):388.
[56]上官海娟,徐江,汤剑青,等.当归对心肌梗塞后心肌细胞凋亡及凋亡相关基因的影响[J]武汉大学学报:医学版,2005,26(2):172-175.
[57]殷惠军,张颖,蒋跃绒,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[J]中国中西医结合杂志,2005,25(3):232-234.
[58]李敏,王硕仁,赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响[J].中西医结合心脑血管病杂志,2005,3(1):33-35.
[59]Bian GX,LiGG,Yang Y,el al.Madecassoside reduces ischemiareperfusioninjury on regional ischemia induced heart infarction in rat[J].Biol PharmBull,2008,31(3):458-463.
[60]Ling H, Lou Y.Total flavones from Elsholtzia blanda reduce infarct sizeduring acute myocardial ischemia by inhibiting myocardial apoptosis inrats[J].J Ethnopharmacol,2005,101(1-3):169-175.
[61]Townsend PA,Scarabelli TM,Pasini E,et al.Epigallocatechin-3-gallateinhibits STAT-1activation and protects cardiac myocytes fromischemia/reperfusion-induced apoptosis[J].FASEB J,2004,18(13):1621-1623.
[62]Zhou L,Xie Y X,Li J,et al.Protective effects of luteolin-7-O-β-D-glucopyranoside on hypoxic-ischemic injuryof myocardial cells in neonatalrats[J].Trad Chin Drug Res Clin Pharmacol,2008,19(4):259-261.
[63]红梅,朝鲁门,斯庆格,等.丹蒌片对心肌梗死大鼠心肌bcl-2,caspase-3表达的影响[J].中国实验方剂学杂志,2012,18(4):216-219.
[64]Tang YL,Zhao Q,Qin X,et al.Paracyline action enhances the effects ofoutologous mesenchymal stem cell transplantation on vascular regenerationin tat model of myocardial infarction[J].Ann Thorac Surg.2005,80(1):229-237.
[65]Berry M F, Engler A J, Woo Y J, et al. Mesenchymal stem cell injectionafter myocardial infarction improves myocardial compliance[J]. Am JPhysiol Heart Circ Physiol,2006,290(6): H2196-2203.
[66]张哲,杨关林,李峥,等.同种异体骨髓间充质干细胞穴位移植对梗死心肌及周围区细胞凋亡及相关蛋白的影响[J].中国组织工程研究与临床康复,2008,12(43):8477-8480.
[67]罗智博,李铮,苑新悦,等.同种异体骨髓间充质干细胞穴位移植1天与7天对急性心肌梗死后心肌细胞凋亡的对比研究[J].中华中医药学刊,2009,28(7):1364-1368.
[68]齐晓云.丹参联合骨髓间充质干细胞移植对兔急性心肌梗死后胶原重构及心功能的影响[D].辽宁中医药大学,2009.
[69]曾彬,林国生,张艳,等.血红素氧合酶-1修饰的骨髓间充质干细胞心肌移植对梗死后心肌细胞凋亡及左心室功能的影响[J].中国病理生理学杂志,2009,25(9):1681-1685.
[70]Li H L, Zhuo M L, Wang D, et al.Targeted cardiac overexpression of A20improves left ventricular performance and reduces compensatory hypertrophyafter myocardial infarction[J]. Circulation,2007,115(14):1885-1894.
[71]Rong S L, Lu Y X, Liao Y H, et al. Effects of transplantedmyoblaststransfected with human growth hormone gene on improvement of ventricularfunction of rats[J]. Chin Med J (Engl),2008,121(4):347-354.
[72]Kaiser R A, Bueno O F, Lips D J, el al. Targeted inhibition of p38mitogen-activated protein kinase antagonizes cardiac injury and cell deathfollowing ischemia-reperfusion in vivo[J]. J Biol Chem,2004,279(15):15524-15530.
[73]Tenhunen O, Soini Y, Ilves M, et al. p38Kinase rescues failingmyocardium after myocardial infarction: evidence for angiogenic andanti-apoptotic mechanisms[J]. FASEB J,2006,20(11):1907-1909.
[74]杨娅,刘广霞.“冬病夏治”穴位敷贴防治肺系疾病的机理探讨[J].针灸临床杂志,2009,25(8):38.
[75]赵欲晓.穴位贴敷治疗慢性支气管炎500例.上海针灸杂志,2005,24(4):3.
[76]瞿群威,袁申平.火针配合穴位敷贴治疗咳喘105例.上海针灸,2001,20(3):12.
[77]顾成光,陈丽萍.穴位贴敷治疗慢性支气管炎472例临床观察.现代康复,2000,4(3):390.
[78］Lin G,Chan S S-K,Li S L,et al. Chemistry and Biological Activitiesof Naturally Occurring Phthalides in Studies in Natural Products Chemistry［J］.Bioactive Natural Products(Part L),2006,32:611-669.
[79］Zhang X Z,Xiao H B,Xu Q,et al.Characterization of phthalides inLigusticum chuanxiong by liquid chromatographic-atmospheric pressurechemical ionization-massspectrometry ［J］. J Chromatogr Sci,2003,41(8):428-433.
[80］郭志峰,王磊,郭婷婷,等.川芎超声浸提物的GCMS分析［J］.河北大学学报(自然科学版),2009,29(2):177-183.
[81］Li Y H,Peng S L,Zhou Y,et al.吴琦,杨秀伟.国家中药材GAP基地产川芎挥发油化学成分的GC-MS分析［J］.中国中药杂志,2008,33(3):276-280.
[82］Miao C P,Wu S H,Luo B Z,et al. A new sesquiterpenoid from Ligusticumchuanxiong Hort［J］.Fitoterapia,2010,(81):1088-1090.
[83]Lim L S,Shen P,Gong Y H,et al. Dimeric progestins from rhizomes ofLigusticum chuanxiong ［J］.Phytochemistry Phytochemistry,2006,(67):728-734.
[84]郝淑娟,张振学,田洋,等.川芎化学成分研究［J］.中国现代中药,2010,12(3):22-25,38.
[85] Li S L,Yan R,Tam Y K,et al. Post-harvest alteration of the main chemicalingredients in Ligusticum chuanxiong Hort.(Rhizoma Chuanxiong)［J］. ChemPharm Bull,2007,55:140-144.
[86]郑汉臣,蔡少青.药用植物学与生药学［M］.第4版.北京:人民卫生出版社,2006:284.
[87]Wai C L, H u I Z, M ichael H, et al. Anxiolytic-lik e action oforallyadm in istered dl-tetrahydropalm atine in elevated plus-maze[J]. ProgNeuro-psychopharm acol Biol Psychiat,2003,67(27):775-779.
[88]贺凯,高建莉,赵光树.延胡索化学成分、药理作用及质量控制研究进展[J].中草药,2007,38(12):1909-1912.
[89]刘嘉,蔡小军,狄留庆.延胡索全碱注射液对麻醉犬血流动力学的影响[J].中国现代药物应用,2008,2(7):6-8.
[90]王胜春,刘明义.当归、莪术、延胡索及其相互配伍对兔胸主动脉条的作用[J].中国现代应用药学杂志,2005,22(1):25-28.
[91]赵昕,汤浩.脱氢紫堇碱对正常和低氧豚鼠心肌细胞内钙的影响[J].中国应用生理学杂志,2003,19(3):222-225.
[92]黄衍寿,李荣.延胡索碱预处理对缺血再灌注心肌钙泵及钠钾泵活性的影响
[C].第八次全国中西医结合心血管病学术会议,2007.
[93]郑杭生,冯年平,陈佳,等．乳香没药的提取工艺及其提取物的镇痛作用［J］．中成药,2006,24(11):956-959．
[94] Lian X N, Zhang L. Prevent ion and cure of coronary hear disearse usingmyrrh[J].Shanxi J Chin Tradit Med,2002,18(4):10.
[95] Ye J H.Th e realize of pharmacological act ion and clinic applicationof mastic and myrrh[J].Clin J Anhui Tradit ChinMed,2003,15(3):264-265.
[96]高海成,孙波,苗春生.大剂量盐酸异丙肾上腺素诱发大鼠心肌缺血性坏死模型的建立[J].中国生物制品学杂志2009,22(3):288-296.
[97]高申.现代药物新剂型新技术[M].北京:人民军医出版社,2002:288-290.
[98]罗世英,陈华萍.透皮吸收常用的几种实验动物,中国药业,2004,13(4):74-75.
[99]Acikel M,Buyukokuroglu ME,Erdogan F,et al.Protective effects ofdantrolene against myocardial jinjury induced by isoproterenol inrats:biochemical and histological findings.Inter JCardiol,2005,98:389-394.
[100]Vimal V,Devaki T.Linear furanocoumarin protects rat myocardium aginstlipidperoxidantion dan membrane danmage during experimental myocardialinjury.Biomedi Pharmacother,2004,58:393-400.
[101]Prabhu S,Narayan S,Devi CS.Mechan ism of protect ive action of mangiferin on supp ress ion of in flamm atory response and lysosom alinstab il ity in ratm odel ofmyocardial infarction[J].Phytoth er Res,2009,23(6):756-760.
[102]高海成,孙波,苗春生,等.大剂量盐酸异丙肾上腺素诱发大鼠心肌缺血性坏死模型的建立[J].中国生物制品学杂志,2009,22(3):288-290,296.
[103]中华医学会心血管病学分会中华心血管病杂志编辑委员会.急性ST段抬高型心肌梗死诊断和治疗指南[J].中华心血管病杂志,2010,38(8):675-690
[104]Thygesen K,Alpert JS, White HD,et al.Universal definition ofmyocardial infarctionJ Am Coll Cardiol.2007Nov27;50(22):2173-95.
[105]陶贵周,姚书霞.2010年我国急性ＳＴ段抬高型心肌梗死诊断与治疗指南解读评析[J].医学与哲学(临床决策论坛版),2011,32(12):22-24,28.
[106]周玖瑶,孙毅东,谭永恒,等.环维黄杨星D对结扎大鼠冠状动脉致心肌缺血的影响[J].中药材.2007,30(7):828-830.
[107] Souza JR,Oliveira RT,Blot ta MH,et al. Serum levels of interl eukin-6(IL-6),int erleu kin-18(IL-18) and C-reactive protein (CRP) in patientswith type-2diabetes and acut ecoronary syndrome without ST-segmentelevation [J].Arq Bras Cardiol,2008,90(2):86-90.
[108]Min N,Paul L,Peter L.Inflammatory cy tokines and postmyocardialinfarction remodeling[J].Circ Res,2004,94:1543-1545.
[109]Ba J,Friedman PA.Calc ium-sensing receptor regu la tion of renalminera lion transport[J].Cell Calcium,2004,35(3):229-237.
[110] ZhangWH,Fu SB,Lu FH,et al.Involvem ent of calcium-sensing receptorin ischem ia/reperfusion-induced apoptosis in rat cardiomyocytes[J].Biochem Biophys Res Commun,2006,347(4):872-881.
[111]Sun YH,Liu MN,Li H,et al.Calcium-sensing receptor induces ratneonatal ventricular cardiom yocyte apoptosis[J].Biochem Biophys ResCommun,2006,350(4):942-948.
[112] Wang LN,W ang C, Lin Y, et al.Involvem en t of calcium-sensingreceptor in cardiac hypertrophy-induced by angiotensin II throughcalcineur in pathway in cultured neonatal rat cardiom yocytes[J].B iochemB iophys Res Commun,2008,369(2):584-589.
[113]郭津,徐长庆,李鸿珠,等.动脉粥样硬化对大鼠心肌钙敏感受体的表达和细胞凋亡的影响[J].中华心血管病杂志,2008,36(12):1101-1105.
[114]郭津,徐长庆,李鸿珠,等.异丙肾性心肌梗死大鼠钙敏感受体的表达和凋亡通路变化[J].中国病理生理杂志,2009,25(1):48-53.
[115]徐长庆,张伟华.心血管系统钙敏感受体的研究进展[J].中国病理生理杂志,2010,26(2):409-413.
[116]孙婷婷,朱铁兵,邵旭武.钙敏感受体在缺氧复氧大鼠心肌细胞凋亡中的作用[J].南京医科大学学报(自然科学版),2009,29(1):45-49.
[117]Venketaraman V,Talane MT,Dayaram YK,et al. Nitric oxide regulationofL-arginine uptake in murine end humanmicrophages[J]Tuberculosts(Edinh),2003,83(5):311-318.
[118]Volz TJ,Schenk JO.L–arginine increascs dopamine transporteractitvity in rat atrianm via a nitric oxide synthase-dependent mechanism[J].Synapse,2004,54(3):173-182.
[119]Mayhan WG,Arrick DM,Sharpe GM,et al． Nitric oxide synthase dependentresponsesof the basilar artery during acute infusion of nicotine［J］.Nicotine TobRes,2009,11(3):270-277.
[120]Moncada S,Palmer RM.Nitric oxide:physiology,pathophysiology andpharmacology［J］.Pharmacology,1991,43(2):109-142.
[121]Higashi Y,Noma K,Yoshizumi M,et al.Endothelial function andoxidativestress in cardiovascular diseases［J］.Circ J,2009,73(3):411-418．
[122]Kapaia MR,Eng JW,Jiang Q,et al.Nitric oxide regulates the26Sproteasome in vascular smooth muscle cells ［J］.NitricOxide,2009,20(4):279-288.
[123]Panaro MA,Brandonisio O,Acquafredda A,et al.Evidences for iNOSexpression and nitric oxide production in the human macrophages［J］．CurrDrug Targets Immune Endocr Metabol Disord,2003,3(3):210-221．
[124]Gao J,Zhao WX,Zhou LJ,et al.Protective effects of propofol onlipopolysaccharide-activated endothelial cell barrier dysfunction［J］.Inflamm Res,2006,55(9):385-392.
[125]路东风,覃军.诱生型一氧化氮合酶基因在心肌梗死大鼠中的表达,广州医学院学报,2003,31(9):54-56.
[126]闫丽萍,庄毓蓝,陈伟民.异丙肾上腺素诱导的急性心肌损伤大鼠一氧化氮系统的变化.中国心血管病研究杂志,2006,4(7):539-541.
[127]Colombo MG,Paradosi U,Andreassi MG,et al.Endothelial notric oxidesynthase gene polymorphisms and risk of coronary artery disease[J].Clinchem,2003,59(3):389-395.
[128]Yoshimura T,Hisatomi A,Kajihara S,etal.The relationship betweeninsulin rasistance and polymorphisms of thendothelial nitric oxidesynthase gene in patients with coronary artery disease[J].J AtherosclerThromb,2003,10(1):43-47.
[129]吴伟康,杨仕云,刘筱霭.心肌缺血时NO代谢的动态变化[J].中国病理生理杂志,2002,8(10):1258-1261.
[130]张齐好,陆大祥,王华东,等.甘氨酸对心肌缺血-再灌注小鼠一氧化氮系统和Bcl-2mRNA表达的影响[J].中国病理生理杂志,2004,20(1):42-46.
[131] Antoniacles C,Tousoulis D,Vasiliadou C,et al.Genetic polymorphismon endothelial niteic oxide synthase affects endothelial activation andinflammatory response during the acute phase of myocardial infarction[J].JAm Coll Cardiol,2005,46(6):1101-1109.
[132]崔华,范利,封志纯,等.缺氧性肺动脉高压对左心室心肌细胞凋亡的影响及心肌Ang含量的相关分析[J].心肺血管病杂志,2006,(1):28.
[133]MacEwan D J. TNF receptor subtype signaling:differences and cellularconsequences[J].Cell Signal,2002,14:477-492.
[134]Laugwitz KL,Moretti A,Weig HJ,et al.Blocking caspase-tivatedapoptosis improves contractility in failing myocardium[J].Hum GeneTner,2001,12(17):2051-2063.
[135]成军.现代细胞凋亡分子生物学[M].北京:科学技术出版社,2012,6:137.
[136]张建文,郭政.曲马多预先给药对急性心肌缺血大鼠心肌P物质的影响[J].山西医科大学学报,2012,43(3):167-170.
[137]郑筱萸.中药新药临床研究指导原则[M].中国医药科技出版社,2002.
[138]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.不稳定性心绞痛和非ST段抬高心梗诊断和治疗指南[J].中华心血管病杂志,2007,4(35):295.
[2]陈维.心绞痛贴膏外治冠心病稳定性心绞痛(痰浊痹阻证)的临床疗效观察.辽宁中医药大学.2010.
[3]清·吴尚先,理论骈文,北京,中国中医药出版社,1995年:50.
[4]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001,23(12):864-867.
[5]赵明地,王凤荣.穴位贴敷治疗冠心病心绞痛理论基础探要[J].实用中医内科杂志,2010,24(4):33-34.
[6]殷建明,罗陆一,张大创等.通心贴穴位外治冠心病心绞痛临床研究[J].中西医结合心脑血管病杂志,2009,7(10):1138-1140.
[7]韩亚男.中药穴位敷贴对心肌缺血大鼠心肌酶的影响[J].上海中医药大学学报,2001,15(3):58-59.
[8]刘新国,周莉玲,郭丽蓉等.环维黄杨星D透皮贴剂抗心肌缺血作用的研究[J].时珍国医国药,2010,21(11):2723-2725.
[9]张颖,孙操.冠心舒贴的抗心肌缺血的实验研究[J].黑龙江医药,2007,20(3):230-231.
[10]李建宇,李怡,龚海英等.蕨麻正丁醇提取部位对小鼠急性心肌缺血损伤的保护作用[J].中西医结合学报,2009,7(1):48-52.
[11]修颖.冠心膏内服配合冠心贴贴敷治疗冠心病稳定型劳累性心绞痛的临床观察[J].河北中医,2010,32(7):981-983.
[12]姜明华.冠心药膜治疗冠心病稳定性心绞痛临床观察[J].中医药学刊,2006,24(10):1959-1960.
[13]柏业军.张培影运用通络保心贴治疗不稳定性心绞痛的经验[J].中医药临床杂志,2010,22(7):617-618.
[14]李根,陈鹏毅,邢洁等.护心贴外敷心俞内关穴治疗冠心病心绞痛临床观察[J].山西中医,2008,24(10):27-28.
[15]华浩明,王家骜,姚祖培等.宁心膏透皮给药治疗冠心病心绞痛50例临床研究[J].中医杂志,2004,45(11):834-835,851.
[16]江武.通痹散穴位贴敷治疗冠心病50例临床观察[J].光明中医,2007,22(12):80-81.
[17]吴泽铭,邢洁,张大创等.通心贴外敷心俞穴对冠心病心绞痛NO、NOS、SOD、MDA的影响[J].河南中医学院学报,2007,22(4):35-36.
[18]邢洁.通心贴外敷心俞与内关穴治疗冠心病心绞痛临床观察[J].山西中医,2007,23(4):62-63.
[19]冯润芬,罗陆一.通心贴心俞穴外敷治疗冠心病心绞痛60例临床观察[J].中国中医药科技,2005,12(1):47-48.
[20]殷建明,罗陆一,张大创等.通心贴穴位外治冠心病心绞痛临床研究[J].中西医结合心脑血管病杂志,2009,7(10):1138-1140.
[21]罗陆一,冯润芬,吴泽民等.温肾化痰活血法心腧穴位外治治疗冠心病心绞痛观察[J].中医药学刊,2006年,24(6):984-985.
[22]宋丽君.心痛散内服外用治疗缺血型冠心病心绞痛120例[J].中国中医药信息杂志,2002,9(11):42.
[23]周建中.克心痛药膜穴位贴敷治疗冠心病心绞痛临床疗效观察[J].江苏临床医学杂志,2002,6(6):599.
[24]高云,高晓光.通心膏贴敷穴位治疗冠心病心绞痛61例疗效观察[J].山西中医学院学报,2007,8(4):25-26.
[25]姜爱平,谢任禹,栗欣等.中药穴位敷贴治疗冠心病心绞痛临床观察[J].中国中医药信息杂志,2003,10(1):41-42.
[26]张俊.自制保心膏治疗冠心病心绞痛48例临床观察[J].中西医结合心脑血管病杂志,2003,1(4):231.
[27]李洪韬.中药贴敷配合外洗治疗冠心病合并高血压病45例[J].中医外治杂志,2008,17(4):13.
[28]Chen YF,Kobayashi S,Chen J,et al.Short term triiodo-L-thyroninetreatment inhibits cardiac myocyte apoptosis in border area aftermyocardial infarction in rats [J].J Mol Cell Cardiol,2008,44(1):180-187.
[29]Gu X,Cheng L,Chueng W L, et al. Neovascularization of IschemicMyocardium by Newly Isolated Tannins Prevents Cardiomyocyte Apoptosis andImproves Cardiac Function[J]. MolMed,2006；12(11-12):275-283.
[30]姚玉宇,马根山,刘乃丰,等.急性心肌梗死后凋亡和炎症及相关因子的动态变化[J].江苏医药,2008,34(12):1271-1273.
[31]王学颖,王阶,杨戈,等.血塞通软胶囊对心肌梗死大鼠血流动力学及心肌细胞凋亡的影响[J].中西医结合学报,2010,8(3):269-274.
[32]王学颖,杨戈,王阶,等.溶血磷脂酸及其受体在急性心肌梗死早期大鼠心肌细胞凋亡调控中的作用及活血方药干预的研究[J].中华中医药杂志,2010,25(12):1999-2002
[33]郭艳,殷惠军,史大卓,等.心脑舒通胶囊对高脂血症大鼠心肌梗死后心肌细胞凋亡及Bax、 Bcl-2蛋白表达的影响[J].中国中西医结合杂志,2006,26(6):541-544.
[34]陈跃峰,杨跃进,阮英茆,等.大鼠急性心肌梗死后心肌细胞凋亡和半胱天冬蛋白酶-3的表达及卡维地洛的防治作用[J].中国循环杂志2004,19(6):454-458.
[35]肖骏,马渝,邓松柏,等.芪苈强心对心肌梗死后犬鼠心肌细胞凋亡的影响[J].中国病理生理杂志,2012,28(6):1045-1050.
[36]Sinagra G,Bussani R,Abbate A, et al.Left ventricular diastolic fillingpattern at Doppler echocardiography and apoptotic rate in fatal acutemyocardial infarction [J].American Journal of Cardiology,2007；99(3):307–309．
[37] Olivetti G,Quaini F,Sala R,et al．Acute myocardial infarction inhumans is associated with activation of programmed myocyte cell death inthe surviving portion of the heart．Mol Cell Cardiol,1996；28(9):2005–2016．
[38]James T N． The variable morphological coexistence of apoptosis andnecrosis in human myocardial infarction: significance for understandingits pathogenesis, clinical course, diagnosis and prognosis． CoronaryArtery Disease,1998；9(5):291–308．
[39]Bardales RH, Hailey LS, Xie SS,et al．In situ apoptosis assay for thedetection of early acute myocardial infarction [J].American Journal ofPathology,1996；149(3):821–829．
[40]Ogino A,Takemura G, Kanamori H.Amlodipine inhibits granulation tissuecell apoptosis through reducing calcineurin activity to attenuatepostinfarction cardiac remodeling: Am-J-Physiol-Heart-Circ-Physiol.2007Oct;293(4): H2271-80.
[41]陈跃峰,杨跃进,陈曦.β受体阻滞剂阿替洛尔和酒石酸美托洛尔对大鼠急性心肌梗死后心肌细胞凋亡及凋亡相关基因表达的作用[J].中国医学科学院学报2006,28(4)538-543.
[42]Feng QZ,Wei LX,Yi J,et al.Relationship between the expression ofFas,bcl-2and apoptosis of cardiomyccytes in experimental myocardialischemia in rats[J].Zonghua Bing Li Xue Za Zhi,2004,33(2):151-154.vonHarsdorf R.Fas-ten your seat belt:anti-apoptotic treatment in heartfailure takes off[J].Circ Rec,2003,95(6):554-556.
[43]Contini P,GhioM,Merlo A,et al.Apoptosis of antigen-specific Tlymphocytes upon the engagement of CD8by soluble HLA calss I moleculesif Fas ligand/Fas mediated:evidence for the involvement of p56lck,calciumcalmodulin kinase II,and Calcium-independent protein kinase C signalingpathways and for NF-kappaB and NF-AT nuclear traslocation[J].JImmunol,2005,175(11):7244-7254.
[44]麦炜颐,马莉,黄裕立,等.ACE抑制剂Ramipril对大鼠急性心肌梗死后心肌细胞凋亡和左室重构的影响[J].中山大学学报(医学科学版),2008,29(5):550-555.
[45]Huang YL,Kuang J,Hu YZ,et al. Bone marrow stromal cell transplantationcombined with angiotensin-converting enzyme inhibitor treatment in ratwith acute myocardial infarction and the role of insulin-like growthfactor-1. Cytotherapy.2012May;14(5):563-9.
[46]Maack C, Kartes T, Kilter H.Oxygen free radical release in human failingmyocardium is associated with increased activity of rac1-GTPase andrepresents a target for statin treatment.
[47]叶强,陈良海,刘应才.辛伐他汀通过Akt/GSK3β通路抑制心肌梗死后心肌细胞凋亡[J].中国药理学通报,2011,27(12):1656-1660.
[48]HM,M llmann H,Hilpert P,et al.Activated cell survivalcascade protectscardiomyocytes from cell death in Tako-Tsubo cardiomyopathy［J］.Eur J HeartFail,2009,11(8):758-64．
[49]Muslin AJ.Akt2:A critical regulator of cardiomyocyte survival andmetabolism［J］.Pedi Card,2011(32):317-22．
[50]DeBosch B,Sambandam N,Weinheimer C,et al.Akt2regulates cardiacmetablism and cardiomyocyte survival ［J］.J Biol Chem,2006,281(43):32841-51．
[51]许香梅,任晓敏,刘曙光.醛固酮受体拮抗剂对急性心肌梗死大鼠心肌细胞凋亡的影响临床荟萃2012,27(14):1230-1233.
[52]叶周恒,杨玉鹤,许骥,等.醛固酮诱导心室重构作用及机制[J].心肺血管病杂志,2011,30(2):174-176.
[53]Hayashi H,Kobara M,Abe M.Aldosterone nongenomically produces NADPHoxidase-dependent reactive oxygen species and induces myocyte apoptosis.Hypertens Res,200831(2):363-75.
[54]夏勇,张勇,李东野,等.塞来昔布对心肌梗死后心肌细胞凋亡的影响中国病理生理杂志,2007,23(1):49-52.
[55]张勇,夏勇,李东野.硝酸异山梨酯对心肌梗死后心肌细胞凋亡的影响[J].中华心血管病杂志,2004,32(2):388.
[56]上官海娟,徐江,汤剑青,等.当归对心肌梗塞后心肌细胞凋亡及凋亡相关基因的影响[J]武汉大学学报:医学版,2005,26(2):172-175.
[57]殷惠军,张颖,蒋跃绒,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[J]中国中西医结合杂志,2005,25(3):232-234.
[58]李敏,王硕仁,赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响[J].中西医结合心脑血管病杂志,2005,3(1):33-35.
[59]Bian GX,LiGG,Yang Y,el al.Madecassoside reduces ischemiareperfusioninjury on regional ischemia induced heart infarction in rat[J].Biol PharmBull,2008,31(3):458-463.
[60]Ling H, Lou Y.Total flavones from Elsholtzia blanda reduce infarct sizeduring acute myocardial ischemia by inhibiting myocardial apoptosis inrats[J].J Ethnopharmacol,2005,101(1-3):169-175.
[61]Townsend PA,Scarabelli TM,Pasini E,et al.Epigallocatechin-3-gallateinhibits STAT-1activation and protects cardiac myocytes fromischemia/reperfusion-induced apoptosis[J].FASEB J,2004,18(13):1621-1623.
[62]Zhou L,Xie Y X,Li J,et al.Protective effects of luteolin-7-O-β-D-glucopyranoside on hypoxic-ischemic injuryof myocardial cells in neonatalrats[J].Trad Chin Drug Res Clin Pharmacol,2008,19(4):259-261.
[63]红梅,朝鲁门,斯庆格,等.丹蒌片对心肌梗死大鼠心肌bcl-2,caspase-3表达的影响[J].中国实验方剂学杂志,2012,18(4):216-219.
[64]Tang YL,Zhao Q,Qin X,et al.Paracyline action enhances the effects ofoutologous mesenchymal stem cell transplantation on vascular regenerationin tat model of myocardial infarction[J].Ann Thorac Surg.2005,80(1):229-237.
[65]Berry M F, Engler A J, Woo Y J, et al. Mesenchymal stem cell injectionafter myocardial infarction improves myocardial compliance[J]. Am JPhysiol Heart Circ Physiol,2006,290(6): H2196-2203.
[66]张哲,杨关林,李峥,等.同种异体骨髓间充质干细胞穴位移植对梗死心肌及周围区细胞凋亡及相关蛋白的影响[J].中国组织工程研究与临床康复,2008,12(43):8477-8480.
[67]罗智博,李铮,苑新悦,等.同种异体骨髓间充质干细胞穴位移植1天与7天对急性心肌梗死后心肌细胞凋亡的对比研究[J].中华中医药学刊,2009,28(7):1364-1368.
[68]齐晓云.丹参联合骨髓间充质干细胞移植对兔急性心肌梗死后胶原重构及心功能的影响[D].辽宁中医药大学,2009.
[69]曾彬,林国生,张艳,等.血红素氧合酶-1修饰的骨髓间充质干细胞心肌移植对梗死后心肌细胞凋亡及左心室功能的影响[J].中国病理生理学杂志,2009,25(9):1681-1685.
[70]Li H L, Zhuo M L, Wang D, et al.Targeted cardiac overexpression of A20improves left ventricular performance and reduces compensatory hypertrophyafter myocardial infarction[J]. Circulation,2007,115(14):1885-1894.
[71]Rong S L, Lu Y X, Liao Y H, et al. Effects of transplantedmyoblaststransfected with human growth hormone gene on improvement of ventricularfunction of rats[J]. Chin Med J (Engl),2008,121(4):347-354.
[72]Kaiser R A, Bueno O F, Lips D J, el al. Targeted inhibition of p38mitogen-activated protein kinase antagonizes cardiac injury and cell deathfollowing ischemia-reperfusion in vivo[J]. J Biol Chem,2004,279(15):15524-15530.
[73]Tenhunen O, Soini Y, Ilves M, et al. p38Kinase rescues failingmyocardium after myocardial infarction: evidence for angiogenic andanti-apoptotic mechanisms[J]. FASEB J,2006,20(11):1907-1909.
[74]杨娅,刘广霞.“冬病夏治”穴位敷贴防治肺系疾病的机理探讨[J].针灸临床杂志,2009,25(8):38.
[75]赵欲晓.穴位贴敷治疗慢性支气管炎500例.上海针灸杂志,2005,24(4):3.
[76]瞿群威,袁申平.火针配合穴位敷贴治疗咳喘105例.上海针灸,2001,20(3):12.
[77]顾成光,陈丽萍.穴位贴敷治疗慢性支气管炎472例临床观察.现代康复,2000,4(3):390.
[78］Lin G,Chan S S-K,Li S L,et al. Chemistry and Biological Activitiesof Naturally Occurring Phthalides in Studies in Natural Products Chemistry［J］.Bioactive Natural Products(Part L),2006,32:611-669.
[79］Zhang X Z,Xiao H B,Xu Q,et al.Characterization of phthalides inLigusticum chuanxiong by liquid chromatographic-atmospheric pressurechemical ionization-massspectrometry ［J］. J Chromatogr Sci,2003,41(8):428-433.
[80］郭志峰,王磊,郭婷婷,等.川芎超声浸提物的GCMS分析［J］.河北大学学报(自然科学版),2009,29(2):177-183.
[81］Li Y H,Peng S L,Zhou Y,et al.吴琦,杨秀伟.国家中药材GAP基地产川芎挥发油化学成分的GC-MS分析［J］.中国中药杂志,2008,33(3):276-280.
[82］Miao C P,Wu S H,Luo B Z,et al. A new sesquiterpenoid from Ligusticumchuanxiong Hort［J］.Fitoterapia,2010,(81):1088-1090.
[83]Lim L S,Shen P,Gong Y H,et al. Dimeric progestins from rhizomes ofLigusticum chuanxiong ［J］.Phytochemistry Phytochemistry,2006,(67):728-734.
[84]郝淑娟,张振学,田洋,等.川芎化学成分研究［J］.中国现代中药,2010,12(3):22-25,38.
[85] Li S L,Yan R,Tam Y K,et al. Post-harvest alteration of the main chemicalingredients in Ligusticum chuanxiong Hort.(Rhizoma Chuanxiong)［J］. ChemPharm Bull,2007,55:140-144.
[86]郑汉臣,蔡少青.药用植物学与生药学［M］.第4版.北京:人民卫生出版社,2006:284.
[87]Wai C L, H u I Z, M ichael H, et al. Anxiolytic-lik e action oforallyadm in istered dl-tetrahydropalm atine in elevated plus-maze[J]. ProgNeuro-psychopharm acol Biol Psychiat,2003,67(27):775-779.
[88]贺凯,高建莉,赵光树.延胡索化学成分、药理作用及质量控制研究进展[J].中草药,2007,38(12):1909-1912.
[89]刘嘉,蔡小军,狄留庆.延胡索全碱注射液对麻醉犬血流动力学的影响[J].中国现代药物应用,2008,2(7):6-8.
[90]王胜春,刘明义.当归、莪术、延胡索及其相互配伍对兔胸主动脉条的作用[J].中国现代应用药学杂志,2005,22(1):25-28.
[91]赵昕,汤浩.脱氢紫堇碱对正常和低氧豚鼠心肌细胞内钙的影响[J].中国应用生理学杂志,2003,19(3):222-225.
[92]黄衍寿,李荣.延胡索碱预处理对缺血再灌注心肌钙泵及钠钾泵活性的影响
[C].第八次全国中西医结合心血管病学术会议,2007.
[93]郑杭生,冯年平,陈佳,等．乳香没药的提取工艺及其提取物的镇痛作用［J］．中成药,2006,24(11):956-959．
[94] Lian X N, Zhang L. Prevent ion and cure of coronary hear disearse usingmyrrh[J].Shanxi J Chin Tradit Med,2002,18(4):10.
[95] Ye J H.Th e realize of pharmacological act ion and clinic applicationof mastic and myrrh[J].Clin J Anhui Tradit ChinMed,2003,15(3):264-265.
[96]高海成,孙波,苗春生.大剂量盐酸异丙肾上腺素诱发大鼠心肌缺血性坏死模型的建立[J].中国生物制品学杂志2009,22(3):288-296.
[97]高申.现代药物新剂型新技术[M].北京:人民军医出版社,2002:288-290.
[98]罗世英,陈华萍.透皮吸收常用的几种实验动物,中国药业,2004,13(4):74-75.
[99]Acikel M,Buyukokuroglu ME,Erdogan F,et al.Protective effects ofdantrolene against myocardial jinjury induced by isoproterenol inrats:biochemical and histological findings.Inter JCardiol,2005,98:389-394.
[100]Vimal V,Devaki T.Linear furanocoumarin protects rat myocardium aginstlipidperoxidantion dan membrane danmage during experimental myocardialinjury.Biomedi Pharmacother,2004,58:393-400.
[101]Prabhu S,Narayan S,Devi CS.Mechan ism of protect ive action of mangiferin on supp ress ion of in flamm atory response and lysosom alinstab il ity in ratm odel ofmyocardial infarction[J].Phytoth er Res,2009,23(6):756-760.
[102]高海成,孙波,苗春生,等.大剂量盐酸异丙肾上腺素诱发大鼠心肌缺血性坏死模型的建立[J].中国生物制品学杂志,2009,22(3):288-290,296.
[103]中华医学会心血管病学分会中华心血管病杂志编辑委员会.急性ST段抬高型心肌梗死诊断和治疗指南[J].中华心血管病杂志,2010,38(8):675-690
[104]Thygesen K,Alpert JS, White HD,et al.Universal definition ofmyocardial infarctionJ Am Coll Cardiol.2007Nov27;50(22):2173-95.
[105]陶贵周,姚书霞.2010年我国急性ＳＴ段抬高型心肌梗死诊断与治疗指南解读评析[J].医学与哲学(临床决策论坛版),2011,32(12):22-24,28.
[106]周玖瑶,孙毅东,谭永恒,等.环维黄杨星D对结扎大鼠冠状动脉致心肌缺血的影响[J].中药材.2007,30(7):828-830.
[107] Souza JR,Oliveira RT,Blot ta MH,et al. Serum levels of interl eukin-6(IL-6),int erleu kin-18(IL-18) and C-reactive protein (CRP) in patientswith type-2diabetes and acut ecoronary syndrome without ST-segmentelevation [J].Arq Bras Cardiol,2008,90(2):86-90.
[108]Min N,Paul L,Peter L.Inflammatory cy tokines and postmyocardialinfarction remodeling[J].Circ Res,2004,94:1543-1545.
[109]Ba J,Friedman PA.Calc ium-sensing receptor regu la tion of renalminera lion transport[J].Cell Calcium,2004,35(3):229-237.
[110] ZhangWH,Fu SB,Lu FH,et al.Involvem ent of calcium-sensing receptorin ischem ia/reperfusion-induced apoptosis in rat cardiomyocytes[J].Biochem Biophys Res Commun,2006,347(4):872-881.
[111]Sun YH,Liu MN,Li H,et al.Calcium-sensing receptor induces ratneonatal ventricular cardiom yocyte apoptosis[J].Biochem Biophys ResCommun,2006,350(4):942-948.
[112] Wang LN,W ang C, Lin Y, et al.Involvem en t of calcium-sensingreceptor in cardiac hypertrophy-induced by angiotensin II throughcalcineur in pathway in cultured neonatal rat cardiom yocytes[J].B iochemB iophys Res Commun,2008,369(2):584-589.
[113]郭津,徐长庆,李鸿珠,等.动脉粥样硬化对大鼠心肌钙敏感受体的表达和细胞凋亡的影响[J].中华心血管病杂志,2008,36(12):1101-1105.
[114]郭津,徐长庆,李鸿珠,等.异丙肾性心肌梗死大鼠钙敏感受体的表达和凋亡通路变化[J].中国病理生理杂志,2009,25(1):48-53.
[115]徐长庆,张伟华.心血管系统钙敏感受体的研究进展[J].中国病理生理杂志,2010,26(2):409-413.
[116]孙婷婷,朱铁兵,邵旭武.钙敏感受体在缺氧复氧大鼠心肌细胞凋亡中的作用[J].南京医科大学学报(自然科学版),2009,29(1):45-49.
[117]Venketaraman V,Talane MT,Dayaram YK,et al. Nitric oxide regulationofL-arginine uptake in murine end humanmicrophages[J]Tuberculosts(Edinh),2003,83(5):311-318.
[118]Volz TJ,Schenk JO.L–arginine increascs dopamine transporteractitvity in rat atrianm via a nitric oxide synthase-dependent mechanism[J].Synapse,2004,54(3):173-182.
[119]Mayhan WG,Arrick DM,Sharpe GM,et al． Nitric oxide synthase dependentresponsesof the basilar artery during acute infusion of nicotine［J］.Nicotine TobRes,2009,11(3):270-277.
[120]Moncada S,Palmer RM.Nitric oxide:physiology,pathophysiology andpharmacology［J］.Pharmacology,1991,43(2):109-142.
[121]Higashi Y,Noma K,Yoshizumi M,et al.Endothelial function andoxidativestress in cardiovascular diseases［J］.Circ J,2009,73(3):411-418．
[122]Kapaia MR,Eng JW,Jiang Q,et al.Nitric oxide regulates the26Sproteasome in vascular smooth muscle cells ［J］.NitricOxide,2009,20(4):279-288.
[123]Panaro MA,Brandonisio O,Acquafredda A,et al.Evidences for iNOSexpression and nitric oxide production in the human macrophages［J］．CurrDrug Targets Immune Endocr Metabol Disord,2003,3(3):210-221．
[124]Gao J,Zhao WX,Zhou LJ,et al.Protective effects of propofol onlipopolysaccharide-activated endothelial cell barrier dysfunction［J］.Inflamm Res,2006,55(9):385-392.
[125]路东风,覃军.诱生型一氧化氮合酶基因在心肌梗死大鼠中的表达,广州医学院学报,2003,31(9):54-56.
[126]闫丽萍,庄毓蓝,陈伟民.异丙肾上腺素诱导的急性心肌损伤大鼠一氧化氮系统的变化.中国心血管病研究杂志,2006,4(7):539-541.
[127]Colombo MG,Paradosi U,Andreassi MG,et al.Endothelial notric oxidesynthase gene polymorphisms and risk of coronary artery disease[J].Clinchem,2003,59(3):389-395.
[128]Yoshimura T,Hisatomi A,Kajihara S,etal.The relationship betweeninsulin rasistance and polymorphisms of thendothelial nitric oxidesynthase gene in patients with coronary artery disease[J].J AtherosclerThromb,2003,10(1):43-47.
[129]吴伟康,杨仕云,刘筱霭.心肌缺血时NO代谢的动态变化[J].中国病理生理杂志,2002,8(10):1258-1261.
[130]张齐好,陆大祥,王华东,等.甘氨酸对心肌缺血-再灌注小鼠一氧化氮系统和Bcl-2mRNA表达的影响[J].中国病理生理杂志,2004,20(1):42-46.
[131] Antoniacles C,Tousoulis D,Vasiliadou C,et al.Genetic polymorphismon endothelial niteic oxide synthase affects endothelial activation andinflammatory response during the acute phase of myocardial infarction[J].JAm Coll Cardiol,2005,46(6):1101-1109.
[132]崔华,范利,封志纯,等.缺氧性肺动脉高压对左心室心肌细胞凋亡的影响及心肌Ang含量的相关分析[J].心肺血管病杂志,2006,(1):28.
[133]MacEwan D J. TNF receptor subtype signaling:differences and cellularconsequences[J].Cell Signal,2002,14:477-492.
[134]Laugwitz KL,Moretti A,Weig HJ,et al.Blocking caspase-tivatedapoptosis improves contractility in failing myocardium[J].Hum GeneTner,2001,12(17):2051-2063.
[135]成军.现代细胞凋亡分子生物学[M].北京:科学技术出版社,2012,6:137.
[136]张建文,郭政.曲马多预先给药对急性心肌缺血大鼠心肌P物质的影响[J].山西医科大学学报,2012,43(3):167-170.
[137]郑筱萸.中药新药临床研究指导原则[M].中国医药科技出版社,2002.
[138]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.不稳定性心绞痛和非ST段抬高心梗诊断和治疗指南[J].中华心血管病杂志,2007,4(35):295.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |