不同剂量法舒地尔对压力负荷心力衰竭大鼠心肌细胞凋亡和凋亡相关基因表达的影响

目的从细胞凋亡角度探讨不同剂量法舒地尔(fasudil)对升主动脉缩窄压力超负荷心力衰竭大鼠的影响及作用机制。方法采用升主动脉缩窄术建立大鼠心力衰竭模型。观察不同剂量fasudil治疗心力衰竭时对心肌细胞凋亡指数(AI)、bcl-2、c-myc蛋白表达水平的影响。结果fasudil干预心功能不全可以使心肌细胞凋亡指数降低,使bcl-2蛋白表达水平上调,c-myc蛋白表达水平降低,且剂量大时效果更明显。结论fasudil能有效减少心力衰竭大鼠心肌细胞凋亡指数,使bcl-2蛋白表达水平上调,c-myc蛋白表达水平降低,防治心力衰竭,这是其治疗心力衰竭的重要机制之一,且剂量大时更明显。

Effects of Fasudil at Different Doses on Cardiomyocyte Apoptosis and Protein Expression Levels of bcl-2,c-myc in the Rats with Pressure Overloaded Heart Failure

Objective To study the mechanisms of action of fasudil at different doses on the cardiomyocyte apoptosis in the rats with pressure overloaded heart failure following coarctation of the ascending aorta.Methods A rat model of heart failure was created by coarctation of ascending aorta.40 female Wistar rats with heart failure were divided randomly into four groups,including natrium chloride (0.1 mL),fasudil(1 mg/kg),fasudil(5 mg/kg),fasudil(20 mg/kg)(n=10 per group),which were treated by i.p injection b.i.d for 4 weeks.Another 10 age-matched sham-operated rats were used as control.The rats were observed for another 20 weeks after coarctation of the ascending aorta operation.Hemodynamic parameters,ratio of LV weight to body weight,cardiomyocyte apoptosis,protein expression levels of bcl-2 and c-myc were investigated in all the groups.Results Fasudil intervention reduced cardiomyocyte apoptosis,decreased protein expression level of c-myc and improved protein expression level of bcl-2 in rats with chronic cardiac dysfunction,in a dose-dependent manner.The number of cardiomyocyte apoptosis and the protein expression level of cmyc were significantly lower and the level of bcl-2 was markedly higher in the group of high dose fasudil than those in the groups of low dose fasudil.Conclusions Fasudil can effectively decrease cardiomyocyte apoptosis,reduce the protein level of c-myc and increase bcl-2 protein level dose-dependently,which may be one of mechanisms of prevention and treatment of heart failure.