黄芪甲苷对慢性心衰大鼠心肌纤维化及能量代谢的影响

目的:研究黄芪甲苷对慢性心衰大鼠心肌纤维化的影响,初步探讨其具体机制。方法:采用腹主动脉缩窄法(AAC)建立大鼠慢性心衰模型,建模成功后随机分为模型组、缬沙坦组及黄芪甲苷组,另建立假手术组。缬沙坦组和黄芪甲苷组分别给予2 mg·kg~(-1)·d~(-1)的缬沙坦及30 mg·kg~(-1)·d~(-1)的黄芪甲苷灌胃,假手术组及模型组给予生理盐水灌胃。8周后收集心脏结构及血流动力学参数,留取心肌染色后观察心肌细胞形态学变化Western blot和RT-qPCR检测长链脂酰辅酶A脱氢酶(LCAD)、6-磷酸果糖激酶1(PFK1)的蛋白及mRNA表达情况。结果:与假手术组相比,模型组大鼠的左室质量指数(LVMI)、胶原容积分数(CVF)、左室后壁厚度(LVPWD)、PFK1蛋白及mRNA表达均升高(P0.05),LCAD蛋白及mRNA表达均下降(P0.05)。与模型组相比,缬沙坦组及黄芪甲苷组LVMI、CVF、LVPWD、PFK1蛋白及mRNA表达均下降(P0.05),LCAD蛋白及mRNA表达升高(P0.05)。结论:黄芪甲苷可以抑制慢性心衰大鼠心肌纤维化,其机制可能是通过上调LCAD、下调PFK1、纠正能量代谢异常实现的。

Effects of astragaloside IV on myocardial fibrosis and energy metabolism in chronic heart failure rats

AIM: To observe the effects of astragaloside IV (AS-IV) on myocardial fibrosis in chronic heart failure (CHF) rats and to explore the underlying mechanism preliminarily. METHODS: Chronic heart failure model rats established by abdominal aorta constriction (AAC) were divided into CHF group, valsartan group and AS-IV group. Sham operation group was also established. The rats in valsartan group and AS-IV group received valsartan and AS-IV at 2 and 30 mg·kg^-1·d^-1, respectively. The rats in sham operation group and CHF group received normal saline. After 8 weeks of treatment, the cardiac structure and the hemodynamic parameters were measured. The morphologic changes of myocardial tissue were observed after staining. The expression of long-chain acyl-CoA dehydrogenase (LCAD) and 6-phosphofructokinase-1 (PFK1) at mRNA and protein levels was determined by RT-qPCR and Western blot. RESULTS: Compared with sham operation group, left ventricular mass index (LVMI), collagen volume fraction (CVF), left ventricular posterior wall depth (LVPWD), and the mRNA and protein of PFK1 in CHF group were increased (P<0.05), while the mRNA and protein levels of LCAD were decreased (P<0.05). Compared with CHF group, the LVMI, CVF, LVPWD, and the mRNA and protein levels of PFK1 in valsartan group and AS-IV group were decreased (P<0.05), while the mRNA and protein levels of LCAD were increased (P<0.05).CONCLUSION: AS-IV inhibits myocardial fibrosis in the CHF rats, the mechanism of which might be associated with up-regulating the expression of LCAD, down-regulating the expression of PFK1 and normalizing the myocardial energy metabolism.