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-phosphofructoki-nase-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 .%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(P<0.05),LCAD蛋白及mRNA表达均下降(P<0.05).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(P<0.05),LCAD蛋白及mRNA表达升高(P<0.05).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.
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