益气活血法治疗冠心病心绞痛血管内皮功能障碍的临床研究
|
摘要
目的：
本课题通过采用对冠心病内皮功能疗效评价的指标进行严格的临床设计，通过测定具有益气活血的补阳还五汤治疗冠心病心绞痛治疗前后ET-1，NO，vWF，FMD的变化，来论证补阳还五汤对改善CHD患者临床症状，改善预后的意义，进而更加科学的评价其对CHD的治疗效果，同时对于CHD的中药治疗客观评价有重要意义。
方法：
选择随机单盲对照的试验方案进行研究。纳入符合冠心病心绞痛诊断标准，属于气虚血瘀型的患者共60例，按照1：1的比例随机分组成治疗组和对照组，在给予基础治疗的基础上再分别给予补阳还五汤及安慰剂治疗，疗程为3周。在治疗前后观察心绞痛症状、心电图疗效、中医症候以及内皮指标的变化。
结果：
心绞痛疗效：补阳还五汤组心绞痛积分有明显改善(P＜0.01)，对照组治疗后积分虽有所下降但与治疗前比较无统计学差异(P＞0.05)，治疗后补阳还五汤组改善程度明显优于对照组(P＜0.05)。心绞痛临床疗效方面治疗组的总有效率为90％，明显优于对照组的66.67％，两组差异具有显著性差异(P＜0.01)。
心电图疗效：治疗组和对照组心电图的总有效率分别为86.7％和56.7％，两组差异具有显著性差异(P＜0.05)。
中医症候：两组中医证候积分均有明显改善(P＜0.05)，尤以治疗组改善程度明显优于对照组(P＜0.01)。中医症候临床疗效方面治疗组总有效率为90.0％，明显优于对照组的66.7％，两组差异具有显著性差异(P＜0.01)。
ET、NO变化：对照组治疗后虽然ET比治疗前略有下降，NO略有升高，但变化无显著性差异(P＞0.05)，治疗组用补阳还五汤后ET比治疗前下降，NO比治疗前升高，两者均由显著性差异(P＜0.01)。治疗后补阳还五汤组的ET水平显著低于对照组(P＜0.01)，治疗后补阳还五汤组的NO水平较对照组有明显升高(P＜0.05)。
vWF变化：治疗前两组vWF水平无显著性差异，治疗组用补阳还五汤后vWF水平比治疗前明显下降(P＜0.05)，治疗后补阳还五汤组vWF水平明显低于对照组(P＜0.05)，而对照组治疗后虽然vWF比治疗前略有下降，但无统计学差异(P＞0.05)。
FMD变化：两组无论从同组治疗前后或者是组间治疗前后比较均无显著性差异(P＞0.05)。
结论：
补阳还五汤能有效改善冠心病患者心电图疗效；补阳还五汤既能有效减少心绞痛发作，又能改善中医证候群，无明显毒副作用；补阳还五汤是通过下调ET水平，同时上调NO水平，抑制vWF释放的作用从而使受损的血管内皮功能得以部分恢复。
Objective: To validate clinicalcurative effect that Buyang Huanwu Decoction improveclinical symptom and prognosis in patients of coronary heart disease through testingthe level of ET-1, NO, vWF in serum and FMD.
Method: This is a single-blind, randomized, matched controlled trial. 60 patients thatwere diagnosed as coronary angina pectoris and qixu xueyu symdrome wererandomly grouped to treatment group and controlled group. Each group had 30 cases.The two groups were treated with Buyang Huanwu Decoction and placebo separatelyon the basis of basical treatment by 3 weeks continuously. After 3 weeks, we observedthe change of ET-1, NO, vWF, FMD, EKG reading, clinical symptoms of anginapectoris, and Chinese medical symptoms.
Result:
Clinical symptoms of angina curative effect: Symptoms of angina were improvedeffectively in treatment group, while there was no statistical significance in controlledgroup. Treatment group shown 90％and controlled group shown 66.7％. Theirdifferences had great statistical significance.
EKG curative effect: The EKG curative effect of the two group separately shown86.7％and 56.7％. Their differences had great statistical significance.Chinese medical symptoms curative effect: Chinese medical symptoms wereimproved effectively in two groups, but the treatment group was more improved thancontrolled group. Treatment group shown 90％and controlled group shown 66.7％.Their differences had great statistical significance.
ET, NO: Although the level of ET in serum decreased and the level of NO increased in controlled group, there were no statistical significance. The level of ET decreased,the level of NO increased after treatment in treatment group which had greatstatistical significance. The level of ET in serum was much lower than that ofcontrolled group after treatment. The level of NO in serum was much higher than thatof controlled group after treatment.
vWF: The level of vWF of treatment group was lower than controlled group whichhad statistic significance. Furthermore, the level of vWF was much lower than that ofcontrolled group after treatment. Although the level of vWF of controlled groupdecreased but there was no statistical significance.
FMD: There was no change of FMD in two groups after treatment. There was nochange of FMD alter treatment in the same group.
Conclusion: The results of the experiment show that Buyang Huanwu Decoction caneffectively improve EKG curative effect. It can control angina pectoris attack,improve Chinese medical symptoms without side-effect. By decreasing the level ofET and increasing the level of NO in serum and controlling reversed bloodendothelium function obstacle partly.
本课题通过采用对冠心病内皮功能疗效评价的指标进行严格的临床设计，通过测定具有益气活血的补阳还五汤治疗冠心病心绞痛治疗前后ET-1，NO，vWF，FMD的变化，来论证补阳还五汤对改善CHD患者临床症状，改善预后的意义，进而更加科学的评价其对CHD的治疗效果，同时对于CHD的中药治疗客观评价有重要意义。
方法：
选择随机单盲对照的试验方案进行研究。纳入符合冠心病心绞痛诊断标准，属于气虚血瘀型的患者共60例，按照1：1的比例随机分组成治疗组和对照组，在给予基础治疗的基础上再分别给予补阳还五汤及安慰剂治疗，疗程为3周。在治疗前后观察心绞痛症状、心电图疗效、中医症候以及内皮指标的变化。
结果：
心绞痛疗效：补阳还五汤组心绞痛积分有明显改善(P＜0.01)，对照组治疗后积分虽有所下降但与治疗前比较无统计学差异(P＞0.05)，治疗后补阳还五汤组改善程度明显优于对照组(P＜0.05)。心绞痛临床疗效方面治疗组的总有效率为90％，明显优于对照组的66.67％，两组差异具有显著性差异(P＜0.01)。
心电图疗效：治疗组和对照组心电图的总有效率分别为86.7％和56.7％，两组差异具有显著性差异(P＜0.05)。
中医症候：两组中医证候积分均有明显改善(P＜0.05)，尤以治疗组改善程度明显优于对照组(P＜0.01)。中医症候临床疗效方面治疗组总有效率为90.0％，明显优于对照组的66.7％，两组差异具有显著性差异(P＜0.01)。
ET、NO变化：对照组治疗后虽然ET比治疗前略有下降，NO略有升高，但变化无显著性差异(P＞0.05)，治疗组用补阳还五汤后ET比治疗前下降，NO比治疗前升高，两者均由显著性差异(P＜0.01)。治疗后补阳还五汤组的ET水平显著低于对照组(P＜0.01)，治疗后补阳还五汤组的NO水平较对照组有明显升高(P＜0.05)。
vWF变化：治疗前两组vWF水平无显著性差异，治疗组用补阳还五汤后vWF水平比治疗前明显下降(P＜0.05)，治疗后补阳还五汤组vWF水平明显低于对照组(P＜0.05)，而对照组治疗后虽然vWF比治疗前略有下降，但无统计学差异(P＞0.05)。
FMD变化：两组无论从同组治疗前后或者是组间治疗前后比较均无显著性差异(P＞0.05)。
结论：
补阳还五汤能有效改善冠心病患者心电图疗效；补阳还五汤既能有效减少心绞痛发作，又能改善中医证候群，无明显毒副作用；补阳还五汤是通过下调ET水平，同时上调NO水平，抑制vWF释放的作用从而使受损的血管内皮功能得以部分恢复。
Objective: To validate clinicalcurative effect that Buyang Huanwu Decoction improveclinical symptom and prognosis in patients of coronary heart disease through testingthe level of ET-1, NO, vWF in serum and FMD.
Method: This is a single-blind, randomized, matched controlled trial. 60 patients thatwere diagnosed as coronary angina pectoris and qixu xueyu symdrome wererandomly grouped to treatment group and controlled group. Each group had 30 cases.The two groups were treated with Buyang Huanwu Decoction and placebo separatelyon the basis of basical treatment by 3 weeks continuously. After 3 weeks, we observedthe change of ET-1, NO, vWF, FMD, EKG reading, clinical symptoms of anginapectoris, and Chinese medical symptoms.
Result:
Clinical symptoms of angina curative effect: Symptoms of angina were improvedeffectively in treatment group, while there was no statistical significance in controlledgroup. Treatment group shown 90％and controlled group shown 66.7％. Theirdifferences had great statistical significance.
EKG curative effect: The EKG curative effect of the two group separately shown86.7％and 56.7％. Their differences had great statistical significance.Chinese medical symptoms curative effect: Chinese medical symptoms wereimproved effectively in two groups, but the treatment group was more improved thancontrolled group. Treatment group shown 90％and controlled group shown 66.7％.Their differences had great statistical significance.
ET, NO: Although the level of ET in serum decreased and the level of NO increased in controlled group, there were no statistical significance. The level of ET decreased,the level of NO increased after treatment in treatment group which had greatstatistical significance. The level of ET in serum was much lower than that ofcontrolled group after treatment. The level of NO in serum was much higher than thatof controlled group after treatment.
vWF: The level of vWF of treatment group was lower than controlled group whichhad statistic significance. Furthermore, the level of vWF was much lower than that ofcontrolled group after treatment. Although the level of vWF of controlled groupdecreased but there was no statistical significance.
FMD: There was no change of FMD in two groups after treatment. There was nochange of FMD alter treatment in the same group.
Conclusion: The results of the experiment show that Buyang Huanwu Decoction caneffectively improve EKG curative effect. It can control angina pectoris attack,improve Chinese medical symptoms without side-effect. By decreasing the level ofET and increasing the level of NO in serum and controlling reversed bloodendothelium function obstacle partly.
引文
[1] Hamon M, valet B, Bauters C, et al. Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelitun-dependent acetylcholine induced relaxation after arterial injury[J], Circulation, 1994, 90:1357-1362
[2] Cayatte A J, Palacino JJ, Horten K, et al. Chronic inhibition of nitric oxide production accelerates neointimal formation and impairs endothelial function in hypercholesterolemic rabbits[J]. Artedoscler Thromb, 1994, 14:753-759
[3] Iangford EJ, Brown AS, Wainwright RJ, et al.Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty.Lancet 1994;344 (8935)1458-60
[4] Nishio E, Fukushma K, Shiozaki M, et al. Nitric oxide donor SNAP induces apoptosis in smooth muscle cells through cGMP-independent mechanism. Biochem Biophys Res Commun 1996;221 (1): 163-8
[5] Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-eyelie guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989;83(5): 1774-7
[6] Kariya K, Kawahara Y, Arakis, et al. Antiproliferative action of cyclic GMP-elevating vasodilators in cultured rabbit, aortic smooth muscle cells. Atherosclerosis 1989;80(2);143-7
[7] Gary UC, Hassid A. Nitric oxide-generating vasodilator's inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism. Biochem Biophys Res Commun 1990;171(1):474-9
[8] Nakaki T, Nakayama M, Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmaeol 1990; 189(60):347-53
[9] Provost P, Larn JY, Lacoste L, et al. Endothelium-derived nitric oxide attenuates neutrophil adhesion to endothelium under arterial flow conditions Arterioseler Thromb 1994;14(3):331-5
[10] Takahashi M, Ikeda U, Masuyama J, et al. Nitric oxide attenuates adhesion molecule expression in human endothelial cells. Cytokine 1996; 8 (11): 817-21
[11] Anderson TJ, Gerhard MD, Meredith IT, et al. Systemic nature of endothelial dysfunction in atheroselerosis [J]. Am J Cardiol, 1995, 75(6):71B-74B
[12] Michel Feleton, Endothelial dysfunction: a novel therapeutic target, the alternative EDHF[J]. J Mol cell Cardiol, 1999 31 (61): 15-22
[13] Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms. oxidation, inflammation, and genetics[J]. Circulation, 1995, 91:2488-2496
[14] Cybulsky MI, Gimbrone MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis[J]. Science, 1991, 252:788-791
[15] Schachinger V, Zeiher AM. Quantitative assessment of coronary vasoreactivity in humans in vivo. Importance of baseline vasomotor tone in atherosclerosis. Circulation 1995;92(8):2087-94
[16] Seccombe JF, Schaff HV. Coronary artery endothelial function after myocardial ischemia and reperfusion. Ann Thorae surg 1995;60(3):778-88
[17] Ludmer Pl, Selw yn AP, shook TL, et al. Paradoxical vasoconstriction induced by aeetyloho line in atheroselerotie coronary arteries[J]. N Engl J Med, 1986, 315(17):1046-1051
[18] Anderson TJ. Assessment and treatment of endothelium dysfunction in humans [J]. J Am Coll Cardiol, 1999, 34(3):631-638
[19] Celerrnajer DS, Sorensen KE, Gooch NM, et al. Non-invasive detection of endothelial dysfunction in child and adults at risk of atheroselerosis[J], Lancet, 1992, 340(8828):1111-1115
[20] Maneini GB, Henry GC, Maeaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND(Trial on Reversing Endothelial Dysfunction)Study, Circulation 1996;94(3):258-65
[21] Skyrme RA, OBrien RC, Berry KI, et al. Vitamin E Supplementation improves endothelial function in type (diabetes mellitus a randomized)placebo-controlled study[J], JACC, 2000, 36(1):94-102
[22] Solzbaeh U, Hornig B, Jeserieh M, et al. Vitamin C improves endothelial dysfunction of epieardial coronary arteries in hypertensive patients[J], Circulation, 1997, 96(5):1513-1519
[23] Doniekier JE, Massant PE, Hodeige D, et al. Additional hypotensive effect of endothelin-l receptor antagonism in hypertensive dogs under angiotensin converting enzyme inhibition[J], Cireulation, 1997, 96(4):1250-1256
[24] Ghiadonil, V'trdis A, Magagna A, et al. Effect of the angiotenisn type receptor blocker eandesartan on endothelial function in patients with essential hypertension[J], Hypertension, 2000, 35(2):501-506
[25] Deng YB, Wang DW, Liel, et al. Effects of the angiotenisn receptor antagonist losartan on the response of the left main coronary artery to cold pressor test in patients with essential hypertension as assessed by eehocardiography.
[26] Dupuis J, Tardif JC, lernace K P, et al. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in isehemia and function of the endothelium) trial. Circulation 1999-99(25):3227-33
[27] O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-eoenzyme A reductase inhibition, improves endothelial function within 1 month. Circulation 1997;95(5): 1126-31
[28] 贺敬波．医师进修杂志，1999(4)：33．
[29] 谭效锋．中国中西医结合实用临床急救，1999(2)：56
[30] 施海峰．河北中医，2000(12)：944
[31] 赵华云．湖北中医学院学报，2001(1)：27
[32] 李卫青．山西中医，2000(4)：25．
[33] 周秀娟．江苏医药，2000(7)：524．
[34] 周亚伟．中国中西医结合杂志，1996(8)：483．
[35] 谢梅林．中草药，1999(11)：834．
[36] 刘亚男．中医药研究，2000(2)：36．
[37] 唐其柱．中国中西医结合杂志，1995(9)：539
[38] 李海聪．中国中西医结合杂志，1999(11)：67
[39] 黄敏珍，等．第一军医大学学报，1999(5)：441．
[40] 王万铁，等．中国病理生理杂志，2001(3)：230．
[41] 杨焕斌，林坚，罗陆一．补肾法对冠心病心绞痛患者NO、NOS、ET的影响．中国中医药信息杂志，2006，13(1)：18-20
[42] 李创鹏，杨慧珊，刘培中，张艳玲．加味瓜萎薤白汤对冠心病气滞血瘀证C反应蛋白、内皮素、血液流变学的影响．中国中医药信息杂志，2006，11(12)：1041-1042
[43] 何亚芳．益气活血汤治疗心绞痛30例，中华临床医学杂志，2005，6(3)：96-97
[44] 徐江平，芮耀诚，李铁军．银杏提取物对培养的脑微血管内皮细胞与单核细胞和中性粒细胞粘附的拮抗作用．中国药理学学报，1999，20(5)：4232425
[45] 王洪巨，黄元伟，孙坚，朱朝晖，张磊．通心络胶囊对不稳定型心绞痛患者血管内皮功能的影响．中国中西医结合杂志，2003，23(8)：5872589
[46] 林蓉，刘俊田，李旭，陈葳．川芎嗪对血管内皮细胞损伤的保护作用．中国药理学与毒理学杂志，2000，14(6)：4252429
[47] 李卫萍，孙明，周宏研．高血压患者血管内皮依赖性舒张功能与血清一氧化氮和超氧化物岐化酶的关系．中国动脉硬化杂志，200311(2)：1552158
[48] 庄小梅．活血化瘀方治疗原发性高血压及对血管内皮功能的影响．湖北中医杂志，2003，25(7)：10212
[49] 丘瑞香，贺敬波，蓝军，邝翠仪，刘红健，冯君．心脉通胶囊对冠心病患者心肌缺血总负荷影响及其作用机制探讨．中国中西医结合杂志，2000，20(1)：19221
[50] 陈利国，孙兆贵，王蕾，毛淳，贾振华，陈贵海，等．血瘀证与血管内皮细胞内游离钙浓度关系的实验研究．山东中医药大学学报2001，25(1)：55257
[51] 刘永红，周东，陈友琴，张敏，钟春华，李强，等．大川芎丸各成分对血管内皮细胞钙通道的阻滞作用．华西药学杂志，2002，17(1)19220
[52] 刘宛斌，刘国卿，肖杭，毛霞，吴建平，石云．粉防己碱抑制培养的牛主动脉内皮细胞内向整流钾电位．中国药理学报，2000，21(12)：11152118
[53] 李艳梅，张慧祺，温廷益，鲁彬，郭利平，杨洪涛．补肾复脉液对缺氧内皮细胞eNOSmRNA和ET21mRNA影响的研究．中国中西医结合杂志，2002，22(9)：6802683
[54] 李凤文，刘晓颖，张立石，刘红，潘静华，贾晓元，等．脉复康对高脂血症家兔血管内皮 功能的影响，2003，9(1)：33236
[55] 顾杨洪，张彩英，黄桂秋，王振义．丹参和丹参素对牛内皮细胞抗凝和纤溶功能的影响．上海第二医科大学，1990, 10(3)：2082210
[56] 韩丽蓓，杨惠民，田金洲，盛彤，朱爱华，钟剑，等．丹参决明颗粒对老年高脂血症血管内皮功能及凝血系统的影响．北京中医药大学学报(中医临床版)，2003，10(4)：526
[57] 吴伟，郑晓伟，陈燕，邢福琴，曾定尹．血脂康对血脂和血管内皮细胞活性物质的影响．中国动脉硬化杂志，2003，11(5)：4192422
[58] 李晓春，杨国晶，董宇翔．补阳还五汤对冠心病左室功能影响的观察[J]．白求恩医科大学学报，1995，21(2)：185-186．
[59] 邵敏，刘文华．补阳还五汤治疗冠心病72例[J]．中医药学报，2006，24(3)：522．
[60] 傅风昌．补阳还五汤治疗冠心病心绞痛45例[J]．实用中医内科杂志，2005，19(4)：360-361．
[61] 陈维初．益气活血化瘀法治疗冠心病46例[J]．江西中医药，1996，27(3)：29．
[62] 张尊磊，冯周云．补阳还五汤合硝酸盐制剂治疗冠心病心绞痛[J]．浙江中西医结合杂志，2004，14(9)：529-530．
[63] 曾明．三参饮合补阳还五汤治疗冠心病心绞痛36例[J]．北京中医，1998，3：18-19．
[64] 沈银芳．益气活血、健脾补肾法治疗老年冠心病30例[B]．医药世界，2006，11：18-19．
[65] 张持．补阳还五汤化裁治疗冠心病心绞痛临床观察[J]．吉林中医药，2005，25(5)：16-17
[66] 汪建国．补阳还五汤加减治疗冠心病心绞痛60例疗效观察[J]．实用中医内科杂志，2006，20(2)：167-168．
[67] 李佑新，丁道猛．补阳还五汤加味治疗冠心病心绞痛49例疗效观察[J]．新中医，2003，35(4)：33-34．
[68] 刘志勇，艾书眉．补阳还五汤加味治疗冠心病心绞痛疗效评价[J]．湖北中医学院学报，2000，2(9)：28-29．
[69] 陈亦民．加昧补阳还五汤治疗冠心病心绞痛5l例[J]．中医药临床杂志，2004，16(1)：55-56．
[70] 乔文军，孔敬东，郑学民．补阳还五汤加减治疗冠心病心绞痛临床观察[J]．辽宁中医杂志，2002，29(3)：153．
[71] 刘俊保．补阳还五汤治疗冠心病心绞痛[J]．医药论坛杂志，2004，25(10)：72．
[72] 张华，梁慕筠，马志雄，叶穗林．补阳还五汤治疗冠心病的临床研究及其作用机制探讨[J]．中国中西医结合杂志，1995，15(4)：213-215．
[73] 蔡冬梅，殷胜利，吴伟康．补阳还五汤治疗气虚血瘀型冠心病的临床疗效及血浆中NO含量的改变[J]．现代医学，2004，32(2)：25-28．
[74] 魏陵博．加减补阳还五汤(酒煎法)治疗冠心病的研究[J]．山东中医药大学学报，2002，26(5)：372-374．
[75] 廖展梅，徐泽杰．加味补阳还五汤治疗冠心病合并前列腺增生症80例[J]．湖南中医杂志，2006，28(11)：24．
[76] 刘爱华．中西医结合治疗冠心病心律失常56例[B]．
[77] 孙学刚，张丽华，蔡红兵，赵益业，蔡宇．补阳还五汤对内皮型eNOS启动子活性的影响[J]．山东中医杂志，2005，24(3)：162-165．
[78] 文志斌等．补阳还五汤对凝血酶诱导血管内皮细胞释放NO，vWF，TFPI及表达组织因子的影响[J]．湖南医科大学学报，2002，27(4)：315-318．
[79] 成细华，邓奕辉，梅志刚，丁志高，喻嵘，田道法．补阳还五汤对缺氧．氧内皮细胞ICAM-1mRNA表达影响的研究[J]．湖南中医学院学报，2004，24(2)：4-6．
[80] 陈利国，屈援，葛红颖，胡小勤，聂优爱，何孟栖．补阳还五汤对血瘀证大鼠血管内皮细胞黏附分子表达的影响[J]．中草药，2005，36(5)：706-709．
[81] 刘发益，文志斌，尚改萍，周春生，杨锡平，贺石林，李俊成．补阳还五汤抗家兔动脉粥样硬化形成的实验研究[J]．湖南医科大学学报，2000，25(1)：33-35．
[82] 吴兰珠，缪建华．重用黄芪的补阳还五汤治疗缺血性中风的临床观察．中西医结合实用临床急救，1996，(2)：62-64．
[83] 李玲玲，刘国树，温新华，等．川芎嗪治疗急性左心功能不全疗效观察．中西医结合实用临床急救，1995，(2)：55-57．
[84] 宋军．卒中与血栓的研究现状与进展．中国中西医结合杂志，1993，13(1)：54-55．
[85] 雷载权．中药学．上海：上海科学技术出版社，1995．206-207．
[86] Wanner D D. Cell biolony of von Willebrand factory [J].AnnuRev Cell Biol, 1990, 6(2):217-246.
[87] Sadler J E. Biochemistry and genetics of von Willebrand factor [J].Annu Rev Cell Biol, 1998, 67(4):395-424.
[2] Cayatte A J, Palacino JJ, Horten K, et al. Chronic inhibition of nitric oxide production accelerates neointimal formation and impairs endothelial function in hypercholesterolemic rabbits[J]. Artedoscler Thromb, 1994, 14:753-759
[3] Iangford EJ, Brown AS, Wainwright RJ, et al.Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty.Lancet 1994;344 (8935)1458-60
[4] Nishio E, Fukushma K, Shiozaki M, et al. Nitric oxide donor SNAP induces apoptosis in smooth muscle cells through cGMP-independent mechanism. Biochem Biophys Res Commun 1996;221 (1): 163-8
[5] Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-eyelie guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989;83(5): 1774-7
[6] Kariya K, Kawahara Y, Arakis, et al. Antiproliferative action of cyclic GMP-elevating vasodilators in cultured rabbit, aortic smooth muscle cells. Atherosclerosis 1989;80(2);143-7
[7] Gary UC, Hassid A. Nitric oxide-generating vasodilator's inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism. Biochem Biophys Res Commun 1990;171(1):474-9
[8] Nakaki T, Nakayama M, Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmaeol 1990; 189(60):347-53
[9] Provost P, Larn JY, Lacoste L, et al. Endothelium-derived nitric oxide attenuates neutrophil adhesion to endothelium under arterial flow conditions Arterioseler Thromb 1994;14(3):331-5
[10] Takahashi M, Ikeda U, Masuyama J, et al. Nitric oxide attenuates adhesion molecule expression in human endothelial cells. Cytokine 1996; 8 (11): 817-21
[11] Anderson TJ, Gerhard MD, Meredith IT, et al. Systemic nature of endothelial dysfunction in atheroselerosis [J]. Am J Cardiol, 1995, 75(6):71B-74B
[12] Michel Feleton, Endothelial dysfunction: a novel therapeutic target, the alternative EDHF[J]. J Mol cell Cardiol, 1999 31 (61): 15-22
[13] Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms. oxidation, inflammation, and genetics[J]. Circulation, 1995, 91:2488-2496
[14] Cybulsky MI, Gimbrone MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis[J]. Science, 1991, 252:788-791
[15] Schachinger V, Zeiher AM. Quantitative assessment of coronary vasoreactivity in humans in vivo. Importance of baseline vasomotor tone in atherosclerosis. Circulation 1995;92(8):2087-94
[16] Seccombe JF, Schaff HV. Coronary artery endothelial function after myocardial ischemia and reperfusion. Ann Thorae surg 1995;60(3):778-88
[17] Ludmer Pl, Selw yn AP, shook TL, et al. Paradoxical vasoconstriction induced by aeetyloho line in atheroselerotie coronary arteries[J]. N Engl J Med, 1986, 315(17):1046-1051
[18] Anderson TJ. Assessment and treatment of endothelium dysfunction in humans [J]. J Am Coll Cardiol, 1999, 34(3):631-638
[19] Celerrnajer DS, Sorensen KE, Gooch NM, et al. Non-invasive detection of endothelial dysfunction in child and adults at risk of atheroselerosis[J], Lancet, 1992, 340(8828):1111-1115
[20] Maneini GB, Henry GC, Maeaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND(Trial on Reversing Endothelial Dysfunction)Study, Circulation 1996;94(3):258-65
[21] Skyrme RA, OBrien RC, Berry KI, et al. Vitamin E Supplementation improves endothelial function in type (diabetes mellitus a randomized)placebo-controlled study[J], JACC, 2000, 36(1):94-102
[22] Solzbaeh U, Hornig B, Jeserieh M, et al. Vitamin C improves endothelial dysfunction of epieardial coronary arteries in hypertensive patients[J], Circulation, 1997, 96(5):1513-1519
[23] Doniekier JE, Massant PE, Hodeige D, et al. Additional hypotensive effect of endothelin-l receptor antagonism in hypertensive dogs under angiotensin converting enzyme inhibition[J], Cireulation, 1997, 96(4):1250-1256
[24] Ghiadonil, V'trdis A, Magagna A, et al. Effect of the angiotenisn type receptor blocker eandesartan on endothelial function in patients with essential hypertension[J], Hypertension, 2000, 35(2):501-506
[25] Deng YB, Wang DW, Liel, et al. Effects of the angiotenisn receptor antagonist losartan on the response of the left main coronary artery to cold pressor test in patients with essential hypertension as assessed by eehocardiography.
[26] Dupuis J, Tardif JC, lernace K P, et al. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in isehemia and function of the endothelium) trial. Circulation 1999-99(25):3227-33
[27] O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-eoenzyme A reductase inhibition, improves endothelial function within 1 month. Circulation 1997;95(5): 1126-31
[28] 贺敬波．医师进修杂志，1999(4)：33．
[29] 谭效锋．中国中西医结合实用临床急救，1999(2)：56
[30] 施海峰．河北中医，2000(12)：944
[31] 赵华云．湖北中医学院学报，2001(1)：27
[32] 李卫青．山西中医，2000(4)：25．
[33] 周秀娟．江苏医药，2000(7)：524．
[34] 周亚伟．中国中西医结合杂志，1996(8)：483．
[35] 谢梅林．中草药，1999(11)：834．
[36] 刘亚男．中医药研究，2000(2)：36．
[37] 唐其柱．中国中西医结合杂志，1995(9)：539
[38] 李海聪．中国中西医结合杂志，1999(11)：67
[39] 黄敏珍，等．第一军医大学学报，1999(5)：441．
[40] 王万铁，等．中国病理生理杂志，2001(3)：230．
[41] 杨焕斌，林坚，罗陆一．补肾法对冠心病心绞痛患者NO、NOS、ET的影响．中国中医药信息杂志，2006，13(1)：18-20
[42] 李创鹏，杨慧珊，刘培中，张艳玲．加味瓜萎薤白汤对冠心病气滞血瘀证C反应蛋白、内皮素、血液流变学的影响．中国中医药信息杂志，2006，11(12)：1041-1042
[43] 何亚芳．益气活血汤治疗心绞痛30例，中华临床医学杂志，2005，6(3)：96-97
[44] 徐江平，芮耀诚，李铁军．银杏提取物对培养的脑微血管内皮细胞与单核细胞和中性粒细胞粘附的拮抗作用．中国药理学学报，1999，20(5)：4232425
[45] 王洪巨，黄元伟，孙坚，朱朝晖，张磊．通心络胶囊对不稳定型心绞痛患者血管内皮功能的影响．中国中西医结合杂志，2003，23(8)：5872589
[46] 林蓉，刘俊田，李旭，陈葳．川芎嗪对血管内皮细胞损伤的保护作用．中国药理学与毒理学杂志，2000，14(6)：4252429
[47] 李卫萍，孙明，周宏研．高血压患者血管内皮依赖性舒张功能与血清一氧化氮和超氧化物岐化酶的关系．中国动脉硬化杂志，200311(2)：1552158
[48] 庄小梅．活血化瘀方治疗原发性高血压及对血管内皮功能的影响．湖北中医杂志，2003，25(7)：10212
[49] 丘瑞香，贺敬波，蓝军，邝翠仪，刘红健，冯君．心脉通胶囊对冠心病患者心肌缺血总负荷影响及其作用机制探讨．中国中西医结合杂志，2000，20(1)：19221
[50] 陈利国，孙兆贵，王蕾，毛淳，贾振华，陈贵海，等．血瘀证与血管内皮细胞内游离钙浓度关系的实验研究．山东中医药大学学报2001，25(1)：55257
[51] 刘永红，周东，陈友琴，张敏，钟春华，李强，等．大川芎丸各成分对血管内皮细胞钙通道的阻滞作用．华西药学杂志，2002，17(1)19220
[52] 刘宛斌，刘国卿，肖杭，毛霞，吴建平，石云．粉防己碱抑制培养的牛主动脉内皮细胞内向整流钾电位．中国药理学报，2000，21(12)：11152118
[53] 李艳梅，张慧祺，温廷益，鲁彬，郭利平，杨洪涛．补肾复脉液对缺氧内皮细胞eNOSmRNA和ET21mRNA影响的研究．中国中西医结合杂志，2002，22(9)：6802683
[54] 李凤文，刘晓颖，张立石，刘红，潘静华，贾晓元，等．脉复康对高脂血症家兔血管内皮 功能的影响，2003，9(1)：33236
[55] 顾杨洪，张彩英，黄桂秋，王振义．丹参和丹参素对牛内皮细胞抗凝和纤溶功能的影响．上海第二医科大学，1990, 10(3)：2082210
[56] 韩丽蓓，杨惠民，田金洲，盛彤，朱爱华，钟剑，等．丹参决明颗粒对老年高脂血症血管内皮功能及凝血系统的影响．北京中医药大学学报(中医临床版)，2003，10(4)：526
[57] 吴伟，郑晓伟，陈燕，邢福琴，曾定尹．血脂康对血脂和血管内皮细胞活性物质的影响．中国动脉硬化杂志，2003，11(5)：4192422
[58] 李晓春，杨国晶，董宇翔．补阳还五汤对冠心病左室功能影响的观察[J]．白求恩医科大学学报，1995，21(2)：185-186．
[59] 邵敏，刘文华．补阳还五汤治疗冠心病72例[J]．中医药学报，2006，24(3)：522．
[60] 傅风昌．补阳还五汤治疗冠心病心绞痛45例[J]．实用中医内科杂志，2005，19(4)：360-361．
[61] 陈维初．益气活血化瘀法治疗冠心病46例[J]．江西中医药，1996，27(3)：29．
[62] 张尊磊，冯周云．补阳还五汤合硝酸盐制剂治疗冠心病心绞痛[J]．浙江中西医结合杂志，2004，14(9)：529-530．
[63] 曾明．三参饮合补阳还五汤治疗冠心病心绞痛36例[J]．北京中医，1998，3：18-19．
[64] 沈银芳．益气活血、健脾补肾法治疗老年冠心病30例[B]．医药世界，2006，11：18-19．
[65] 张持．补阳还五汤化裁治疗冠心病心绞痛临床观察[J]．吉林中医药，2005，25(5)：16-17
[66] 汪建国．补阳还五汤加减治疗冠心病心绞痛60例疗效观察[J]．实用中医内科杂志，2006，20(2)：167-168．
[67] 李佑新，丁道猛．补阳还五汤加味治疗冠心病心绞痛49例疗效观察[J]．新中医，2003，35(4)：33-34．
[68] 刘志勇，艾书眉．补阳还五汤加味治疗冠心病心绞痛疗效评价[J]．湖北中医学院学报，2000，2(9)：28-29．
[69] 陈亦民．加昧补阳还五汤治疗冠心病心绞痛5l例[J]．中医药临床杂志，2004，16(1)：55-56．
[70] 乔文军，孔敬东，郑学民．补阳还五汤加减治疗冠心病心绞痛临床观察[J]．辽宁中医杂志，2002，29(3)：153．
[71] 刘俊保．补阳还五汤治疗冠心病心绞痛[J]．医药论坛杂志，2004，25(10)：72．
[72] 张华，梁慕筠，马志雄，叶穗林．补阳还五汤治疗冠心病的临床研究及其作用机制探讨[J]．中国中西医结合杂志，1995，15(4)：213-215．
[73] 蔡冬梅，殷胜利，吴伟康．补阳还五汤治疗气虚血瘀型冠心病的临床疗效及血浆中NO含量的改变[J]．现代医学，2004，32(2)：25-28．
[74] 魏陵博．加减补阳还五汤(酒煎法)治疗冠心病的研究[J]．山东中医药大学学报，2002，26(5)：372-374．
[75] 廖展梅，徐泽杰．加味补阳还五汤治疗冠心病合并前列腺增生症80例[J]．湖南中医杂志，2006，28(11)：24．
[76] 刘爱华．中西医结合治疗冠心病心律失常56例[B]．
[77] 孙学刚，张丽华，蔡红兵，赵益业，蔡宇．补阳还五汤对内皮型eNOS启动子活性的影响[J]．山东中医杂志，2005，24(3)：162-165．
[78] 文志斌等．补阳还五汤对凝血酶诱导血管内皮细胞释放NO，vWF，TFPI及表达组织因子的影响[J]．湖南医科大学学报，2002，27(4)：315-318．
[79] 成细华，邓奕辉，梅志刚，丁志高，喻嵘，田道法．补阳还五汤对缺氧．氧内皮细胞ICAM-1mRNA表达影响的研究[J]．湖南中医学院学报，2004，24(2)：4-6．
[80] 陈利国，屈援，葛红颖，胡小勤，聂优爱，何孟栖．补阳还五汤对血瘀证大鼠血管内皮细胞黏附分子表达的影响[J]．中草药，2005，36(5)：706-709．
[81] 刘发益，文志斌，尚改萍，周春生，杨锡平，贺石林，李俊成．补阳还五汤抗家兔动脉粥样硬化形成的实验研究[J]．湖南医科大学学报，2000，25(1)：33-35．
[82] 吴兰珠，缪建华．重用黄芪的补阳还五汤治疗缺血性中风的临床观察．中西医结合实用临床急救，1996，(2)：62-64．
[83] 李玲玲，刘国树，温新华，等．川芎嗪治疗急性左心功能不全疗效观察．中西医结合实用临床急救，1995，(2)：55-57．
[84] 宋军．卒中与血栓的研究现状与进展．中国中西医结合杂志，1993，13(1)：54-55．
[85] 雷载权．中药学．上海：上海科学技术出版社，1995．206-207．
[86] Wanner D D. Cell biolony of von Willebrand factory [J].AnnuRev Cell Biol, 1990, 6(2):217-246.
[87] Sadler J E. Biochemistry and genetics of von Willebrand factor [J].Annu Rev Cell Biol, 1998, 67(4):395-424.