心复康丸对压力超负荷大鼠心肌miRNA-21的影响

Effect of Xinfukang Pill on Myocardial miRNA-21 of Pressure Overload Rats

目的:观察心复康丸对压力超负荷大鼠所致的心肌肥厚和心室重构的干预作用,并研究其作用机制是否影响心肌组织miRNA-21的表达。方法:雄性Wistar健康大鼠采用腹主动脉缩窄的方法,复制大鼠心肌肥厚和心室重构的模型,随机分为模型组,依那普利组(1.04 mg·kg^(-1)·d^(-1)),心复康丸低、高剂量组(52,208 mg·kg^(-1)·d^(-1))和假手术组,每组20只。分别于术后8,12周采用超声心动评价心功能二尖瓣水平收缩期左室后壁厚度(LVPWs),收缩末期左室容积(LV Vols)及左心室射血分数(LVEF);免疫组织化学法检测心肌组织中Fas,Fas L蛋白表达的变化;实时荧光定量-聚合酶链式反应(Real-time PCR)检测心肌组织miRNA-21 mRNA表达的改变。结果:术后8周,与正常组比较,各手术模型组大鼠LVPWs水平显著升高,LV Vols,LVEF水平显著降低,心脏肥大指数显著增加,心肌组织Fas与Fas L蛋白含量显著增加,miRNA-21 mRNA的表达显著升高(P<0.01);与模型组比较,心复康丸低、高剂量组和依那普利组能明显降低LVPWs水平,明显升高LV Vols,LVEF水平,明显降低心脏肥大指数,明显降低心肌组织Fas与Fas L蛋白的表达,显著提高miRNA-21 mRNA的表达,心复康丸高剂量较为显著(P<0.05,P<0.01)。术后12周,与正常组比较,各手术模型组大鼠LVPWs水平显著升高,LV Vols,LVEF水平显著降低,心脏肥大指数显著增加,心肌组织Fas与Fas L蛋白含量显著增加,miRNA-21 mRNA的表达显著升高(P<0.01);与模型组比较,心复康丸低、高剂量组和依那普利组能明显降低LVPWs水平,明显升高LV Vols,LVEF水平,明显降低心脏肥大指数,明显降低心肌组织Fas与Fas L蛋白的表达,显著提高miRNA-21 mRNA的表达(P<0.05,P<0.01)。结论:心复康丸改善压力超负荷大鼠心功能的作用可能与促进miRNA-21 mRNA的表达,调控Fas,Fas L蛋白,抑制细胞凋亡有关。

Objective： To explore the effect of Xinfukang pill in intervening pressure overload-induced myocardial hypertrophy and ventricular remodeling in rats,and the correlation between its pharmacological effect and the expression of miRNA-21 in cardiac tissue. Method： The abdominal aorta narrowing and contraction method was adopted in adult health male Wistar rats to establish the model of myocardial hypertrophy and ventricular remodeling. Four weeks after coarctation of abdominal aorta,the Wistar rats were randomly divided into model group,Enalapril group（ 1. 04 mg·kg^（-1）·d^（-1））,Xinfukang low and high-dose groups（ 52,208 mg·kg^（-1）·d^（-1））,and and sham group,with 20 in each group. After 8,12 weeks,echocardiographic evaluation was conducted for cardiac indexes,LVPWs,LV Vols and LVEF. The expressions of Fas,Fas L in cardiac tissue were detected by immunohistochemistry,and the expression of miRNA-21 was also detected by Real-time PCR. Result： After eight weeks,compared with normal group,all model groups showed significant increases in LVPWs,cardiomegaly index,Fas and Fas L protein contents,and miRNA-21 mRNA expression,and notable decreases in LV Vols,LVEF（ P〈0. 01）. Compared with normal group,Xinfukang low and high-dose groups and Enalapril group showed remarkable reductions in LVPWs,cardiomegaly index,and Fas and Fas L protein contents,and notable increases in LV Vols,LVEF,and miRNA-21 mRNA expression,particularly in Xinfukang high-dose group（ P〈0. 05,P〈0. 01）. Twelve weeks later,compared with normal group,all of model groups showed significant increases in LVPWs,cardiomegaly index,Fas and Fas L protein contents,and miRNA-21 mRNA expression,and notable decreases in LV Vols,LVEF（ P〈0. 01）. Compared with Enalapril group,Xinfukang high and low-dose groups showed remarkable reductions in LVPWs,cardiomegaly index,and Fas and Fas L protein contents,and notable increases in LV Vols,LVEF,and miRNA-21 mRNA expression（ P〈0. 05,P〈0. 01）. Conclusion： The effect of Xinfukang pill in improving the cardiac function of rats with pressure overload may be correlated with the promotion of the expression of miRNA-21,the regulation of Fas and Fas L,and the inhibition of apoptosis.