葶苈生脉方对充血性心力衰竭大鼠心肌RhoA/ROCK信号通路的干预效应

Intervention Effects of Tingli Shengmai Fang on Signal Pathway of Myocardial RhoA/ROCK in Rats with Congestive Heart Failure

目的:研究葶苈生脉方对充血性心力衰竭(CHF)大鼠左心室肌RhoA、ROCK1、p-MYPT-1及cfos蛋白表达的影响,探讨其防治心肌重塑的作用机制。方法:将健康雄性SD大鼠随机分为5组,假手术组、模型组、葶苈生脉方低剂量组、高剂量组和对照组。除假手术组只分离腹主动脉不结扎外,其余4组采用腹主动脉缩窄法制作CHF大鼠模型。5组均于手术后4周开始灌胃、腹腔注射给药(水),连续8周。停药(水)24 h后迅速股动脉取血及左心室组织剥离,采用放射免疫分析法检测血浆AngⅡ含量,Western Blotting技术测定RhoA、ROCK1、p-MYPT-1及c-fos蛋白的表达。结果:与假手术组比较,模型组大鼠血浆AngⅡ含量,心肌组织RhoA、ROCK1、p-MYPT-1及c-fos蛋白表达均明显增高(P<0.01)。与模型组比较,各给药组大鼠心肌组织RhoA、ROCK1、p-MYPT-1及c-fos蛋白表达均显著降低(P<0.01),葶苈生脉方低剂量组、高剂量组大鼠血浆AngⅡ含量降低(P<0.01)。结论:葶苈生脉方通过调节RhoA/ROCK信号通路,降低RhoA、ROCK1、p-MYPT-1及c-fos蛋白表达,改善心肌重塑,从而有效缓解大鼠CHF。

Objective： to study the effect of Tingli Shengmai Fang on left ventricular muscle RhoA,ROCK1,p-MYPT-1 and cfos protein expression in rats with congestive heart failure（ CHF）,and to investigate its mechanism of prevention and treatment of myocardial remodeling. Methods： Healthy male SD rats were randomly divided into 5 groups： sham operation group,model group,Tingli Shengmai Fang low dose group,high dose group and control group. Except for the dissection of abdominal aorta without ligature in the sham operation group,the abdominal aorta coarctation method was employed to make the CHF rat model of the other 4 groups. The 5 groups were treated with intragastric administration and intraperitoneal injection（ water） for 8 weeks at the 4 th week after the operation.After withdrawal（ water） for 24 h,blood was collected and left ventricular tissue was rapidly removed from femoral artery. Plasma Ang II content was detected by radioimmunoassay. The expression of RhoA,ROCK1,p-MYPT-1 and c-fos protein was detected by Western Blotting. Results： Compared with sham operation group,the level of Ang II and the expression of RhoA,ROCK1,p-MYPT-1 and c-fos protein in myocardial tissue of model group increased significantly（ P 〈 0. 01）. Compared with the model group,RhoA,ROCK1,pMYPT-1 and c-fos protein expression of each administration group were significantly decreased（ P 〈 0. 01）,plasma Ang II levels of Tingli Shengmai Fang low and high dose groups were reduced（ P 〈 0. 01）. Conclusion： Tingli Shengmai Fang can reduce the expression of p-MYPT-1 and c-fos protein and improve myocardial remodeling through regulating the pathway of RhoA/ROCK,RhoA,ROCK1,thus effectively alleviate the rat CHF.