心肌梗死后心衰大鼠心肌细胞凋亡和凋亡相关基因表达的变化

Changes of cardiomyocyte apoptosis and expression of apoptosis-associated gene during heart failure following myocardial infarction in rats

目的 探讨心肌细胞凋亡在充血性心力衰竭 (CHF)发生、发展中的作用 ,Bcl 2和Fas及其配体 (FasL)对心肌细胞凋亡的调控机制。方法 采用心肌梗死 (MI)大鼠模型 ,观察雄性Wistar大鼠MI后 2、4及 8周的血流动力学参数、心室重塑指标、心肌细胞凋亡、Fas、FasL和Bcl 2的mRNA和蛋白表达的改变。结果 MI后 4周大鼠出现平均动脉压、±dp dtmax下降 ,左室舒张末压、右室 体重比增高 ,MI后 8周上述改变更为明显 ;MI后心肌细胞凋亡指数、Fas及FasL的mRNA和蛋白表达逐渐升高 ,Bcl 2的mRNA和蛋白表达下调。结论 心肌细胞凋亡在MI后CHF发生、发展过程中起着重要的作用 ,Fas和FasL表达上调、Bcl 2表达下降介导MI后心肌细胞凋亡的发生。

Objective To study the role of cardiomyocyte apoptosis, and the mechanisms of Fas, Fas ligant (FasL) and Bcl 2 regulating apoptosis in the process of congestive heart failure (CHF). Methods Animal model of myocardial infarction (MI) was inflicted by ligating the left coronary artery of male Wistar rats for 2, 4, and 8 weeks respectively, and the rats with sham operation served as control. Hemodynamics, ventricular remodeling parameters, cardiac myocyte apoptosis, and expressions of Fas, FasL and Bcl 2 mRNAs and proteins were investigated in the experimental and control animals. Results In the rats with ligation for 4 and 8 weeks, their mean arterial pressure and ±dp/dtmax were in a progressive falling, and left ventricular end-diastolic pressure and the ratio of right ventricular weight/body increased. After MI, apoptosis index was increased, expressions of mRNA and protein of Fas and FasL were gradually up-regulated, and expression of Bcl 2 were decreased. Conclusion Myocyte apoptosis may play a pivotal role in the incidence and progression of CHF. The over expression of Fas and FasL, and the suppression of Bcl 2 induce signaling pathways of cardiomyocyte apoptosis.