法舒地尔对急性心肌梗死大鼠血流动力学及相关蛋白表达的影响

目的]探讨法舒地尔对急性心肌梗死（AMI）大鼠血流动力学及相关蛋白表达的影响.方法]取雄性Wistar大鼠,结扎左前降支建立AMI 动物模型,术后24 h存活的大鼠随机分为AMI组、低分子肝素组和法舒地尔组.再随机选取10只大鼠作为假手术组,只在左前降支下穿线不结扎.低分子肝素组4 μL/kg腹腔注射;法舒地尔组给予法舒地尔5 mg/ kg 腹腔注射,2次/日;AMI组和假手术组给予等量生理盐水.4周后分别测血流动力学指标：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）;western blot检测Caspase-3、Bax及Bcl-2表达的变化.结果]AMI组大鼠血流动力学指标与假手术组相比,差异有显著性（P〈0.05）.与AMI组相比,低分子肝素组和法舒地尔组大鼠血流动力学指标改善,相关蛋白Bcl-2 表达增加,Caspase-3、Bax表达减少,差异均有显著性（P〈0.05）.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.

Effect of Fasudil on Hemodynamics and Expression of Associated Proteins in Rats with Acute Myocardial Infarction

Objective] To explore the effect of fasudil on hemodynamics and expression of the associated proteins in rats with acute myocardial infarction（AMI）. Methods] Male Wistar rats were selected, and the left anterior descending artery was ligated to establish the animal models of AMI. The surviving rats at 24h after the operation were divided into AMI group, low molecular weight heparin group and fasudil group. Other 10 rats were randomly selected as sham operation group, which the braid under left anterior descending artery was performed without the ligation. Low molecular weight heparin group was intraperitoneally injected with 4ul/kg low molecular weight heparin. Fasudil group was intraperitoneally injected with 5mg/kg fasudil twice a day. AMI group and the sham group were given the equal volume of normal saline. After 4 weeks, the hemodynamic parameters such as left ventricular systolic pressure（LVSP）, left ventricular end diastolic pressure （LVEDP） and left ventricular pressure maximal rate of rise and fall（＋dp/dtmax, dp/dtmax） were measured. Western blot was used to detect the expression of Caspase-3, Bax and Bcl-2. Results]There was significant difference in the hemodynamic parameters between AMI group and the sham group（ P 〈0.05）. The hemodynamic parameters were improved, and the expression of Bcl 2 increased and the expression of Caspase-3 and Bax decreased in low molecular weight heparin group and fasudil group, and there were significant differences between AMI group and low molecular weight heparin group or fasudil group（ P 〈0.05）. Conclusion] Rho kinase may involve in the myocardial cell apoptosis and the progress of heart failure after AMI. Fasudil can reduce the cell apoptosis, protect ischemic myocardium and delay the process of heart failure through inhibiting the expression of Rho kinas.