曲美他嗪对犬急性心肌梗死后延迟再灌注中缺血区心肌细胞凋亡的影响

Effects of trimetazidine on cardiomyocyte apoptosis in late reperfusion after acute myocardial infarction in canine

目的探讨曲美他嗪(trimetazidine)在犬急性心肌梗死后延迟再灌注中对梗死周边缺血区心肌细胞的保护作用及其机制。方法24只健康成年犬随机平均分为3组:假手术组、单纯延迟再灌注组(late reperfusion group,LR)、延迟再灌注预加曲美他嗪组(late reperfusion+trimetazidinegroup,LR+TMZ)。假手术组和LR组灌服生理盐水,LR+TMZ组灌服曲美他嗪(2mg·kg-1.d-1)共14d。所有犬于d14灌药2h后开胸,假手术组不结扎冠状动脉;LR和LR+TMZ在高位结扎左冠状动脉前降支10h,再灌注10h,制成AMI延迟再灌注模型。采用TUNEL法测心肌细胞凋亡指数(AI),免疫组化法测Bcl-2、Bax、细胞色素C和AIF蛋白表达。结果与LR组相比,LR+TMZ组心肌细胞AI明显降低,Bax、细胞色素C和AIF蛋白的表达明显减少(P<0.01),而Bcl-2蛋白的表达明显增高(P<0.01);分别与假手术组比较,差异均有显著性(P<0.01)。结论曲美他嗪在急性心肌梗死后延迟再灌注中可减少梗死周边缺血区心肌细胞的凋亡,其机制可能与增加Bcl-2蛋白的表达,减少Bax、细胞色素C、AIF蛋白的表达有关。

Aim effects and the To investigate the cardioprotective possible mechanism of trimetazidine in the risky areas during late reperfusion after acute myocardial infarction in canine. Methods Twenty-four adult dogs were randomized into three groups：sham op- eration group （ n = 8 ） ,late reperfusion group （ LR, n = 8）, late reperfusion after trimetazidine treatment group （ LR ＋ TMZ, n = 8 ）. Physiological saline was orally given in the sham operation group and LR group and trimetazidine （2 mg · kg^-1 · d ^-1 ） in the LR ＋ TMZ group for fourteen days. After that later, all chests were opened and coronary areteries were exposed. Exceptly shame operation group, the late reperfusion of acute myocardial infarction model was made by ligating the coronary for 10 h,followed by optotic index were detected reperfusion of 10 h. Ap- by TUNEL. The Bcl-2,Bax, Cytochrome C and apoptosis-inducing factor （AIF） proteins were detected by immunohistochemistry. Results Compared with those of LR group, myocardial apoptotic index and the expression of Bax, Cytochrome C and AIF proteins in LR ＋ TMZ decreased significantly （ all P 〈 0. 01 ）, but the expression of Bcl-2 proteins increased （ P 〈 0. 01 ）. Compared with shame operation group respectively, all indicators were signifi- cantly different （ P 〈 0. 01 ）. Conclusion Trimetazi- dine could decrease cardiomyocyte apoptosis in the risky area during late reperfusion after acute myocardial infarction ,which might be related to the increased expression level of Bcl-2 proteins and decreased expression level of Bax, Cytochrome C and AIF proteins.