大鼠急性心肌梗死后心肌细胞凋亡和半胱天冬蛋白酶-3的表达及卡维地洛的防治作用

Beneficial Effects of Carvedilol on Cardiomyocyte Apoptosis and Caspase-3 Expression After Acute Myocardial Infarction in Rats

目的 :研究大鼠急性心肌梗死后心肌细胞凋亡和半胱天冬蛋白酶 3 (Caspase 3 )的表达及卡维地洛的防治作用。 方法 :冠状动脉结扎术后 2 4h存活的雌性SD大鼠 83只随机分为心肌梗死对照组 (MI组 ,n =43 )和卡维地洛[10mg/(kg·d) ]治疗组 (C组 ,n =40 )两组 ,另设假手术组 (S组 ,n =2 7) ;最终血流动力学资料完整的上述各组大鼠数分别为 11、 13、 9、 15、 10和 10只。C组于术后 2 4h直接灌胃法给药。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法 (TUNEL)和脱氧核糖核酸 (DNA)凝胶电泳检测心肌细胞凋亡。免疫组化方法和Western印迹法检测Cas pase 3的表达。 结果 :与S组相比 ,MI组的左心室收缩压 (LVSP)和左心室内压最大上升和下降速率 (±dp/dt)均显著降低 (P <0 0 5～ 0 0 1) ,左心室舒张末压 (LVEDP)均显著升高 (P <0 0 5～ 0 0 1) ,且 4W时升高更为显著 (P <0 0 1) ;梗死区或疤痕区、梗死边缘区和非梗死区的心肌细胞凋亡指数均显著升高 (P <0 0 5～ 0 0 1) ,Caspase 3表达也均显著增高 (P <0 0 5～ 0 0 1)。与MI组相比 ,C组 48h的LVSP、±dp/dt和心率均显著降低 (P <0 0 5～ 0 0 1) ,但LVEDP及上述各部位的心肌细胞凋亡指数和Caspase 3的表达均无显著变化 ;而C组

Objective:To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and the expression of Caspase 3 after acute myocardial infarction (AMI) in rats. Methods:AMI model was established with the ligation of anterior descending coronary artery in female SD rats. Twenty four hours after operation, 83 survivors were randomly assigned to AMI control (MI, n Z =43) or carvedilol [10 mg/ (kg·d) ] treatment (C, n =40) group,with each being randomly reassigned to 48 hour and 4 week subgroups according to the time points: MI 48 h and MI 4 W, C 48 h and C 4 W. Sham operated (S, n =27) group was selected randomly, and also reassigned to S 48 h and S 4 W subgroups. The final rats number in each subgroup was 11,13,9,15,10,and 10, repectiely. Carvedilol was given to group C by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with TUNEL and DNA ladder. Caspase 3 was detected with immunohistochemistry and Western blot analysis. Results:Compared with sham operated group, in MI 48 h and MI 4 W group, left ventricular systolic pressure (LVSP) and the maximum rate rise of left ventricular pressure (±dp/dt) were significantly decreased ( p <0 05—0 01) ,while left ventricular end diastolic pressure (LVEDP) was significantly increased ( p <0 05) ,even significantly higher at 4 weeks ( p <0 01) .Myocyte apoptotic index was also significantly increased in the infracted/scar, border and non infarcted areas ( p <0 05—0 01) ,with the significantly increased expression of Caspase 3 ( p <0 05—0 01) . Compared with MI group, LVEDP, myocyte apoptotic indices in the three areas and the expression of Caspase 3 were not significantly changed B ( p >0 05) in C 48 h group, only LVSP and ±dp/dt were significantly decreased ( p <0 05—0 01) .In C 4 W group, LVEDP, as well as the myocyte apoptotic indices in the scar and border areas were significantly decreased ( p <0 05—0 01) , but LVSP,±dp/dt and expression of Caspase 3 were not significantly changed ( p >0 05) . Conclusions:As abnormal hemodynamics and left ventricular function developed after AMI in rats, cardiomyocyte apoptosis occurred in the infarction/scar, border and non infarcted areas.Four weeks of carvedilol treatment could improve left ventricular function and reduce cardiomyocyte apoptosis in the scar and border areas.