法舒地尔对心肌急性梗死大鼠心肌组织Bc1-2和Bax表达及血流动力学功能影响

目的探讨法舒地尔对急性心肌梗死(AMI)大鼠心肌组织Bc1-2、Bax表达及血流动力学功能影响。方法选取雄性Wistar大鼠,结扎其左前降支制作AMI模型,将术后24h存活的大鼠随机分为治疗组和AMI组。另随机选取10只大鼠作为假手术组,只在其左前降支下穿线不结扎。治疗组给予法舒地尔5mg/kg腹腔注射,每日2次;AMI组和假手术组给予等量生理盐水。4周后分别测其血流动力学指标左心室收缩压(LVSP),左心室舒张末压(LVEDP),左心室内压最大上升和下降速率(+dp/dtmax、-dp/dtmax);RT-PCR法测定Rho激酶mRNA的表达;免疫组织化学方法测定凋亡相关蛋白Bcl-2及Bax表达的变化。结果AMI组大鼠血流动力学指标、心肌组织Rho激酶mRNA、凋亡相关蛋白Bcl-2及Bax表达与假手术组相比,差异均有显著性(F=14.79～178.79,q=4.85～24.95,P<0.01)。与AMI组相比,治疗组大鼠血流动力学指标改善,心肌组织Rho激酶mRNA表达减少,凋亡相关蛋白Bcl-2表达增加,Bax表达减少,差异均有显著性(q=3.20～15.11,P<0.05、0.01)。结论Rho激酶参与了AMI后心肌细胞凋亡及心力衰竭的进展,法舒地尔通过抑制Rho激酶的表达减少细胞凋亡,保护缺血心肌,延缓心力衰竭进程。

EFFECTS OF FASUDIL ON EXPRESSIONS OF Bcl-2, Bax AND HEMODYNAMICS IN INFARCTED MYOCARDIUM OF RATS

Objective To investigate the effects of fasudil on the expressions of Bcl-2,Bax and the hemodynamics in myocardium of rats with acute myocardial infarction (AMI).MethodsA model of AMI in Wistar rats was created by ligating left anterior descending coronary artery (LAD), for those survived for 24 hours after procedure were randomly divided into treatment group and AMI group. An additional 10 rats served as sham-operation group, the LAD was braided, but not ligated. Rats in trea-tment group were treated with Fasudil (5 mg/kg) intraperitoneally, twice a day, and those in AMI and sham-operation group were administered with equivalent volume of normal saline. Four weeks later, the hemodynamic pararmeters, i.e. left ventricular systo-lic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximum rising and dropping rates of left ventricular pressure (+dp/dtmax, -dp/dtmax) were measured by catheterization. The expression of Rho kinase mRNA was measured by RT-PCR, and expressions of Bcl-2 and Bax protein measured by immunohistochemical staining. ResultsThe differences of hemodynamic pararmeters, expressions of myocardial Rho-kinase mRNA, Bcl-2 and Bax, the apoptosis-related proteins between sham-operation group and AMI were significant (F=14.79-178.79;q=4.85-24.95;P<0.01). Compared with those of AMI group, the hemodynamics of treatment group improved, the expressions of Rho-kinase mRNA and bax decreased, and that of bcl-2 increased (q=3.20-15.11;P<0.05,0.01). ConclusionRho-kinase involvs in the post-AMI myocardial cell apoptosis and the development of heart failure. Fasudil delays the process of heart failure through suppressing Rho expression, decreasing cellapoptosis, and protecting ischemic heart muscle.