BACKGROUND:The therapeutic effect of traditional Chinese drug on myocardial ischemia and reperfusion has been increasingly attached importance to. The tongxinluo, a Chinese paten drug taking insect medicine as its major gradients, has been achieved satisfactory effect in anti-myocardial ischemia clinicallyOBJECTIVE: To investigate the effect of tongxinluo on myocardial apoptosis induced by ischemic reperfusion.DESIGN:A randomized controlled trialSETTING: Department of Traditional Chinese Medicine (TCM) of the First Affiliated Hospital, Sun Yat-sen UniversityMATERIALS:The experiment was conducted from November to December 2002 at the Molecular Medicine Research Center of Sun Yat-sen University.METHODS:Totally 72 Kunming mice were at random divided into 6groups with 12 in each group: 2 g/kg tongxinluo, 1.5 g/kg tongxinluo, 1.0g/kg tongxinluo group (The mice were administrated by gavage, once a day, on the day 5, one hour after administration, pituitrin and nitroglycerin were in combination used for building the myocardial ischemic reperfusion model), isosorbide dinitrade group (The dose was 3.9 g/kg, and the rest treatment was the same as the above), model group and blank control group(Normal saline was taken as substitute for the drug). At the end of trial the myocardia of the mice were taken for investigating the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) of myocardia in mice with ischemic reperfusion, analyzing the myocardial apoptosis index, and determining the expression levels of apoptosis-relevant proteins bcl-2 and bax.MAIN OUTCOME MEASURES: [1] Comparison of SOD activity and MDA level in mice of each group. [2] Comparison of myocardial apoptosis and apoptosis relevant proteins.RESULTS:Totally 72 mice involved were good for the trial and no one died. [1] SOD activity and MDA level: Compared with the model and isosorbide dinitrade groups, SOD activity in 2 g/kg tongxinluo, 1.5 g/kg tongxinluo, 1.0 g/kg tongxinluo group was increased [( 1379.28±140.03 ),(1223.91 ±109.02), (1789.19 ±155.20), (2267.79 ±216.04), (2387.55±229.71 )nkat/L]; MDA level was decreased [(16.58±2.59), (20.40±2.66),(12.73±1.98), (9.65±2.03), (7.56±1.67)nmol/L], and the effect was increased as the dose was raised [2] myocardial apoptosis and apoptosis relevant proteins: Compared with the model and isosorbide dinitrade groups, the myocardial apoptosis index and Bax expression index in 2 g/kg tongxinluo,1.5 g/kg tongxinluo, 1.0 g/kg tongxinluo group were obviously decreased[(13.84±1.97)%, (11.56±1.43 )%, ( 334±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 expression index was obviously increased [(6.22±0.50)%, (8.73 ±0.63)%, (11.38 ±1.38)%, (16.22 ±2.36)%, (19.45±2.92)%], and with a dose-effect relationship.CONCLUSION:Tangible capsule had the effects of. resisting oxygen free radical injury, anti-myocardial apoptosis and protecting ischemic reperfusion myocardial cells, and with a dose dependence.%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1 h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3.9 g/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1 g/kg组、通心络1.5g/kg组、通心络2 g/kg组的超氧化物歧化酶活性升高(1.37928±140.03),(1 223.91±109.02),(1 789.19±155.20),(2 267.79±216.04),(2 387.55±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1 g/kg组、通心络1.5 g/kg组、通心络2 g/kg组的心肌细胞凋亡指数和Bax蛋白表达指数明显降低[(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蛋白表达指数明显升高[(6.22±0.50)%,(8.73±0.63)%,(11.38±1.38)%,(16.22±2.36)%,(19.45±2.92)%],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.
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