通心络对家兔动脉粥样硬化合并急性心肌梗死的保护作用及其机制

The Protective effect of Tongxinluo on the acute myocardial infarction in experimental atherosclerosis model rabbits and initial investigation for its possible mechanism

目的研究通心络对家兔实验性动脉粥样硬化合并急性心肌梗死的保护作用，探讨其可能的作用机制。方法采用高脂饮食建立家兔动脉粥样硬化模型。27只造模成功的家兔随机分成3组，每组9只，分别为安慰剂组（A组）、通心络组（B组）和阳性对照组（c组）。A组予以安慰剂，B组予以通心络0．5g-kg-1d。＋阿司匹林10mg·kg-1·d-1＋阿托伐他汀5mg·kg＋d-1；c组予以阿司匹林10mg·kg-1·d-1＋给药期间普通饮食。各组在常规剂量药物干预1周后以3倍常规剂量的负荷剂量药物干预3h，建立急性心肌梗死模型。急性心肌梗死模型造模成功4h后处死家兔，取心脏标本制作病理切片，观察病理形态学改变。应用免疫组化方法检测缺血心肌组织细胞凋亡相关蛋白Bcl一2、Bax的表达水平；应用TUNEL技术检测心肌细胞凋亡指数。结果与A组比较，B组和c组Bax蛋白的表达水平均显著降低（RO．05），B组Bax蛋白的表达水平最低，Bcl-2蛋白的表达则反之，B组和c组Bcl-2蛋白的表达水平均显著升高（P〈0．05），B组Bcl-2蛋白的表达水平最高；与A组比较，B组和c组心肌细胞凋亡指数下降，但B组心肌细胞凋亡水平明显减轻（P〈0．05）。结论通心络可以通过调节凋亡相关蛋白Bax及Bcl-2的表达，减少缺血心肌组织心肌细胞凋亡，对心肌梗死有保护作用。

Objective To study the protective effect of Tongxinluo on acute myocardial infarction in ex- perimental atherosclerosis model rabbits. Methods The rabbit atherosclerosis models were developed by high cholesterol feeding. Then 27 successful atheroselerosis model rabbits were randomly divided into three groups, the placebo group （group A）, the Tongxinluo group （group B）, the positive control group （group C）, group A was given placebo, group B was given the conventional close of Tongxinluo 0.Sg＇kg-l＇d-1 ＋ aspirin 10 mg＇kg-l-d-l＋ atorvast atin 5 mg＇kgq＇d-l. Group C was given the conventional dose of aspirin 10 mg＇kgq＇d-l＋atorvastatin 5 mg＇kg-l＂d-1, all groups were fed with ordinary diet. After one week , each group was given loading dose, three times of conventional dose at three hours before the acute myocardial infarction model was developed. Four hours later, the rabbits were killed. The myocardial samples were sliced for the pathological observation. The apoptosis related protein expression of Bcl-2 and Bax in ischemic myocardial tissues were measured with immunohistochemical method. Cardiomyocyte apoptosis index was detected using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling（TUNEL）method. Results Compared with group A, the protein expression levels of Bax in both group B and C were significantly reduced （P〈0.05）, and that of group B was the lowest, on the contrary, the protein ex-pression levels of Bcl-2 in both group B and C were significantly increased （P〈0.05）, and that of group B was the highest, compared with group A, cardiomyocyte apoptosis index of both group B and C was significantly decreased, and the cardiomyocyte apoptosis in group C was more obvious than group B （P〈0.05）. Conclusion By regulating of the apoptosis related proteins expression of Bax and Bcl-2 to reduce cardiomyocyte apoptosis in ischemic my- ocardial tissues, Tongxinluo has a protective effect on myocardial infarction.