丹参酮ⅡA对压力负荷增加大鼠心肌肥厚的抑制作用

目的:观察RhoA、Rock1蛋白在压力负荷增加大鼠心肌中的表达,探讨丹参酮ⅡA(tanshinoneⅡA,Tan Ⅱ A)对压力负荷增加大鼠心肌肥厚的抑制作用。方法:40只成年雄性SD大鼠,随机分成5组(n=8),即假手术组(Sham组)、模型组(Model组)、Tan Ⅱ A低剂量组L-Tan Ⅱ A组,10 mg/(kg.d)]、Tan Ⅱ A高剂量组H-Tan Ⅱ A组,20 mg/(kg.d)]及阳性对照药物卡托普利组Captopril组,100 mg/(kg.d)]。除Sham组外,其余4组大鼠均行肾上方腹主动脉缩窄术建立压力负荷增加心肌肥厚模型,Sham组大鼠仅分离腹主动脉而不结扎。术后4周成功造模并开始给药,疗程为4周。8周后,检测心脏肥厚指数和心肌组织病理学,ELISA法检测心肌羟脯氨酸含量以及免疫组化和免疫印迹法检测心肌组织中RhoA和Rock1蛋白的含量。结果:与Sham组比较,Model组大鼠的心脏肥厚指数、心肌羟脯氨酸含量及心肌组织中RhoA和Rock1蛋白含量均显著升高(均P<0.01);与Model组比较,Tan Ⅱ A低剂量组的心脏肥厚指数、心肌羟脯氨酸含量及心肌组织中RhoA和Rock1蛋白含量均降低(均P<0.05),而Tan Ⅱ A高剂量组上述指标均显著降低(均P<0.01)。结论:压力负荷增加大鼠心肌组织中RhoA和Rock1蛋白的表达明显升高,表明RhoA/Rock信号通路参与了压力负荷增加大鼠心肌肥厚的发生与发展。Tan Ⅱ A能抑制RhoA/Rock信号通路,从而改善心肌肥厚。

Protective effect of tanshinone IIA against myocardial hypertrophy in rats with pressure overload

AIM: To observe the changes of RhoA and Rock1 expressions in rat myocardial tissues with pressure overload and to explore the protective effects of tanshinone ⅡA(Tan IIA) against myocardial hypertrophy.METHODS: Thirty-two Sprague Dawley(SD) rats induced by abdominal aorta constriction preparation were randomly divided into four groups(each n=8): model group(P<0.01),Tan ⅡA of low-dose group L-Tan ⅡA group,10 mg/(kg·day)],Tan ⅡA of high-dose group H-Tan IIA group,20 mg/(kg·day)],positive captopril group captopril group,100 mg/(kg·day)] and age-matched SD sham-operated group(n=8) as control.The model of pressure overload-induced myocardial fibrosis was successfully established after 4 weeks of operation.After 4 weeks of Tan ⅡA treatment,heart mass indexes were estimated concurrently with evaluation of myocardial histology as well as myocardial hydroxyproline content by ELISA and immunohistochemistry staining and Western blot for myocardial RhoA and Rock1 content.RESULTS: Compared with those in sham group,heart mass indexes,myocardial hydroxyproline content and myocardial RhoA and Rock1 content were increased in the model group(P<0.01).Compared with those in model group,heart mass indexes,myocardial hydroxyproline content and myocardial RhoA and Rock1 content were decreased in the L-Tan ⅡA group(P<0.05),whereas these indexes were decreased significantly in the H-Tan ⅡA group(P<0.01).CONCLUSIONS: Expressions of RhoA and Rock1 protein significantly increase in pressure overload rat myocardium,indicating that RhoA/Rock signaling pathways are involved in pressure overload in rat cardiac hypertrophy and occurrence and development of cardiac hypertrophy in rats with pressure overload.Tan ⅡA can alleviate cardiac hypertrophy possibly by downregulation of the expression of RhoA/Rock signaling pathways.