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背景:传统中药对心肌缺血-再灌注的治疗作用日益受到重视,以虫类药物为主的中成药通心络在临床抗心肌缺血的治疗中取得了明显的疗效。目的:探讨中药通心络对抗缺血再灌注诱发的心肌细胞凋亡的作用。设计:随机对照观察。单位:中山大学附属第一医院中医科。材料:各项实验于2002-11/12在中山大学分子医学研究中心进行,选择72只雄性昆明种小鼠。方法:72只昆明小鼠随机分成6组,每组12只。通心络2g/kg组、通心络1.5g/kg组、通心络1.0g/kg组(每天灌胃1次,第5天灌药1h后用垂体后叶素和硝酸甘油联用复制心肌缺血再灌注模型方法进行造模)、消心痛组(剂量为3.9g/kg,余处理办法同上)、模型组和空白对照组(用生理盐水代替各药物)。实验结束时取小鼠的心肌,观察小鼠缺血再灌注模型心肌组织超氧化物歧化酶活性、丙二醛水平,分析心肌细胞凋亡指数和凋亡相关蛋白bcl-2,bax表达水平。主要观察指标:①各组小鼠超氧化物歧化酶活性、丙二醛水平比较。②各组小鼠心肌细胞凋亡及凋亡相关蛋白的比较。结果:72只小鼠实验过程中状态符合实验要求,无死亡。①超氧化物歧化酶活性、丙二醛水平:与模型组和消心痛组比较,通心络1g/kg组、通心络1.5g/kg组、通心络2g/kg组的超氧化物歧化酶活性升高(1379.28±140.03),(1223.91±109.02),(1789.19±155.20),(2267.79±216.04),(2387.55±229.71)nkat/L、丙二醛的水平降低(16.58±2.59),(20.40±2.66),(12.73±1.98),(9.65±2.03),(7.56±1.67)nmol/L,而且随着剂量的增大其效率进一步增强。②心肌细胞凋亡及凋亡相关蛋白:与模型组和消心痛组比较,通心络1g/kg组、通心络1.5g/kg组、通心络2g/kg组的心肌细胞凋亡指数和Bax蛋白表达指数明显降低犤(13.84±1.97)%,(11.56±1.43)%,(3.34±0.96)%,(0.82±0.12)%,(0.42±0.06)%;(17.44±6.18)%,(15.45±3.72)%,(10.85±2.73)%,(6.46±1.88)%,(5.57±1.49)%犦,Bcl-2蛋白表达指数明显升高犤(6.22±0.50)%,(8.73±0.63)%,(11.38±1.38)%,(16.22±2.36)%,(19.45±2.92)%犦,且呈量效关系。结论:通心络胶囊具有抗氧自由基损伤、抗细胞凋亡保护缺血后再灌注心肌细胞的作用,而且呈剂量依赖性。
BACKGROUND: The traditional Chinese medicine has become more and more important in the treatment of myocardial ischemia-reperfusion. Traditional Chinese medicine Tongxinluo, which is mainly composed of worms, has achieved remarkable curative effect in the treatment of myocardial ischemia. Objective: To investigate the effect of Tongxinluo on the apoptosis of myocardial cells induced by ischemia-reperfusion. Design: Randomized controlled observations. Unit: Department of Traditional Chinese Medicine, First Affiliated Hospital, Sun Yat-sen University. MATERIALS: Each experiment was performed at the Institute of Molecular Medicine, Sun Yat-sen University from November 2002 to December 12, and 72 male Kunming mice were selected. Methods: 72 Kunming mice were randomly divided into 6 groups, 12 in each group. Tongxinluo 2g/kg group, Tongxinluo 1.5g/kg group, Tongxinluo 1.0g/kg group (once per day, 1st day after 5th day of instillation, 1h after the use of pituitrin and nitroglycerin Myocardial Ischemia-Reperfusion model method was performed to model, isosorbide dinitrate group (dose was 3.9g/kg, remaining treatment method was the same as above), model group and blank control group (saline solution instead of each drug). At the end of the experiment, the myocardium of the mice was taken to observe the activity of superoxide dismutase and the level of malondialdehyde in the myocardium of the mouse model of ischemia-reperfusion, and to analyze the apoptotic index of myocytes and the expression of apoptosis-related proteins bcl-2 and bax. MAIN OUTCOME MEASURES: 1 The activity of superoxide dismutase and the level of malondialdehyde in each group were compared. 2 Comparison of myocardial cell apoptosis and apoptosis-related proteins in each group of mice. RESULTS: The status of 72 mice during the experiment met the experimental requirements and no death occurred. 1 Superoxide dismutase activity and malondialdehyde levels: compared with model group and isosorbide dinitrate group, Tongxinluo 1g/kg group, Tongxinluo 1.5g/kg group, Tongxinluo 2g/kg group superoxide The dismutase activity increased (1379.28±140.03), (1223.91±109.02), (1789.19±155.20), (2267.79±216.04), (2387.55±229.71) nkat/L, and the level of malondialdehyde decreased (16.58±2.59). (20.40±2.66), (12.73±1.98), (9.65±2.03), (7.56±1.67) nmol/L, and their efficiency increased further with increasing dose. 2 Cardiomyocyte Apoptosis and Apoptosis-Related Proteins: Compared with the model group and the isosorbide dinitrate group, the cardiomyocyte apoptosis index of Tongxinluo 1g/kg group, Tongxinluo 1.5g/kg group and Tongxinluo 2g/kg group The Bax protein expression index was significantly decreased by (13.84±1.97)%, (11.56±1.43)%, (3.34±0.96)%, (0.82±0.12)%, (0.42±0.06)%; (17.44±6.18)%, (15.45±3.72)%, (10.85±2.73)%, (6.46±1.88)%, (5.57±1.49)%, Bcl-2 protein expression index was significantly increased (6.22±0.50)%, (8.73±0.63) )%, (11.38 ± 1.38)%, (16.22 ± 2.36)%, (19.45 ± 2.92)% 犦, and the dose-effect relationship. Conclusion: Tongxinluo Capsule has the effects of anti-oxygen free radical damage and anti-apoptosis, which protects cardiomyocytes from ischemia-reperfusion and is dose-dependent.