法舒地尔对急性心肌梗死大鼠心肌的保护作用

Fasudil protects the myocardium in rats with acute myocardial infarction

目的:通过检测急性心肌梗死(AMI)大鼠左心室梗死面积及缺血区凋亡细胞来评价法舒地尔对大鼠AMI后心肌的保护作用。方法:雌性Wistar大鼠随机分为3组,AMI组:结扎左前降支(LAD);治疗组:术前1 h法舒地尔30 mg/kg腹腔注射,结扎LAD;假手术组:仅在LAD下穿线但不结扎。术后24 h,伊文蓝-红四氮唑双染色,确定缺血面积和梗死面积,TUNEL法检测缺血区凋亡细胞,免疫组织化学染色法检测缺血区bcl-2和bax的表达,逆转录-聚合酶链式反应测定Rho激酶mRNA的表达。结果:治疗组与AMI组比较,梗死面积显著减小(26.04±2.51)%∶(32.27±3.07)%,P<0.01,缺血面积差异无统计学意义。AMI组与假手术组比较,凋亡指数明显增加(31.94±3.03)∶(2.44±1.37),P<0.01,bcl-2表达降低,bax表达增加,Rho激酶mRNA表达增加(均P<0.01)。而治疗组与AMI组比较,凋亡指数显著降低,bcl-2表达增加,bax表达降低,Rho激酶mR-NA表达降低,均P<0.01。结论:Rho激酶参与了AMI心肌细胞的凋亡,法舒地尔的心肌保护作用与其抗心肌细胞凋亡效应有关。

Objective：To study the effects of fasudil, a Rho-kinase inhibitor, on protection the myocardium in rats with acute myocardial infarction（AMI）. Method：Twenty-nine female wistar rats were subjected to left anterior descending coronary artery（LAD） ligation and were divided randomly into three groups： sham operation group （not ligation of LAD）, AMI group and treated group. 1 h before surgery the rats were received normal saline 0.5 ml（sham group and AMI group）and 30 mg/kg fasudil（treated group）. At 24 hours after coronary ligation, the rats were sacrificed. The infarct size and ischemia size were determined by evans-hule and TTC double staining. The apoptotic cardiocyte in the ischemia region was determined by TUNEL assay and the apoptotic index（AI） were calculated. The hcl-2 and hax protein expressions were measured by immunohistochemical staining. The Rho-kinase mRNA expression in the ischemia region was measured by RT-PCR. Result： The infarct size was reduced obviously in treated group compared with AMI group（26.04±2. 51）% ： （32. 27±3.07）% ,P〈0.01. The AI significantly increased in AMI group compared with sham group, （31.94 ± 3.03）% ： （2.44 ± 1.37）%, P〈 0.01, and in treated group the AI reduced sharply （ 18.39 ± 1.53） %. The overexpression of Rho-kinase mRNA was attenuated by Rho-kinase. Meanwhile AMI induced downregulation of bcl-2 and upregulation of bax in myocardium was remarkably attenuated in the treated animals. Conclusion： Rho-kinase plays an important role in cardiocyte apoptosis induced by AMI and fasudil provides cardiac protection via anti-apoptotic effect.