缬沙坦对大鼠缺血-再灌注心肌caspase-3活性及凋亡相关基因表达的影响

Effect of valsartan on caspase-3 activity and apoptosis-associated gene expression in myocardial ischemiareperfusion rats

目的：观察缬沙坦对大鼠心肌缺血-再灌注(I/R)时心肌细胞天冬氨酸特异的半胱氨酸蛋白酶-3(caspase-3)活性、Bcl-2和Bax蛋白表达的影响。方法：以SD大鼠建立I/R模型,设立I/R组、缬沙坦组和假手术组。用分光光度法检测caspase-3活性,免疫组化法检测心肌组织Bcl-2和Bax蛋白表达,透射电镜观察心肌超微结构的变化。结果：同I/R组相比,缬沙坦组心肌组织caspase-3活性明显降低(P＜0．05),Bax蛋白表达显著降低(P＜0．01),而Bcl-2蛋白表达显著增高(P＜0．01),Bax/Bcl-2显著降低(P＜0．01),心肌细胞超微结构损伤明显减轻。结论：缬沙坦通过抑制caspase-3活性、调控Bax/Bcl-2表达而抑制心肌I/R所致细胞凋亡。

Objective： To investigate the effect of valsartan on activity of easpase-3 and expression of Bcl-2 and Bax in myocardial isehemia-reperfusion （I/R） rats. Methods： SD rats were randomly divided into three groups：I/R, valsartan and sham group. The activity of caspase-3 was determined by fluorescent analysis, and the expression of Bcl-2 and Bax protein was measured by immunohistochemical technique. The ultrastructural change of the myocardium was observed under electron microscope. Results： Compared with I/R group, the activity of caspase-3 and protein expression of Bax gene markedly decreased in valsartan group（P〈0.05）, but the protein expression of Bcl-2 increased（ P〈0. 01 ）, the positive metric substance of immunohistochemistry was markedly decreased. Pathological changes of myocardial ultrastructure in valsartan group showed relatively minor damage compared with I/R group. Conclusions： Valsartan can inhibit apoptosis induced by myocardial I/R through inhibiting the activity of caspasc 3 and modulating the expression of Bax and Bcl-2 protein.