【摘要】 目的:研究黄芪甲苷对压力超负荷大鼠心室重构的影响,初步探讨其具体机制。方法:8周龄健康SD大鼠采用腹主动脉缩窄法建立压力超负荷模型,术后6周行大鼠超声心动图判断建模是否成功,建模成功后随机分为盐酸贝那普利组、模型对照组、低剂量及高剂量黄芪甲苷组,另建立假手术组,每组20只大鼠,低剂量和高剂量黄芪甲苷组分别给予40 mg/(kg·d)、80 mg/(kg·d)的黄芪甲苷灌胃,盐酸贝那普利组给予10 mg/(kg·d)的盐酸贝那普利灌胃,假手术组及模型对照组给予相同体积的生理盐水灌胃。干预8周后行大鼠超声心动图测定大鼠心脏结构及功能指标,然后行大鼠左心室插管收集血流动力学参数,留取大鼠血液及心肌测定游离脂肪酸(FFA)浓度,留取心肌组织行苏木素伊红(HE)染色、Masson染色观察心肌细胞形态学变化,蛋白免疫印迹(Western blot)、实时定量聚合酶链式反应(qRT-PCR)检测过氧化物酶体增殖物激活受体a(PPARa)蛋白及mRNA表达情况。结果:与假手术组相比,模型对照组大鼠的左心室质量指数、胶原容积分数、FFA浓度增高(P均<0.05~0.01),PPARa蛋白及其mRNA表达明显下降(P均<0.01)。黄芪甲苷干预后,低剂量及高剂量黄芪甲苷组左心室质量指数、胶原容积分数、FFA浓度较模型对照组下降(P均<0.05~0.01),PPARa蛋白及其mRNA表达较模型对照组升高(P均<0.01)。结论:黄芪甲苷可以抑制压力超负荷大鼠心室重构,其机制可能是通过上调PPARa及其mRNA的表达情况,提高心肌FFA利用率,进而改善心肌能量代谢实现的。更多还原

【Abstract】 Objective:To study the impact of astragaloside on ventricular remodeling and peroxisome proliferator activated receptor a(PPARa) expression in pressure-overload rats and to preliminarily explore its mechanism.Methods:Pressure-overload rat’s model was established by abdominal aorta constriction(AAC) in 8-week old SD rats and the result was confirmed by echocardiography at 6 weeks later. Pressure-overload rats were divided into 4 groups with different intragastric treatment:Model control(normal saline) group, Benazepril hydrochloride [10mg/(kg.d)] group, Low-dose astragaloside [40mg/(kg·d)] group and High-dose astragaloside [80mg/(kg.d)] group; in addition, Sham operation group, the rats received intragastricnormal normal saline. n=20 in each group and all animals were treated for 8 weeks. Rat’s cardiac structure and function indexes were assessed by echocardiography, hemodynamic parameter was examined by left ventricular intubation, myocardium and blood levels of free fatty acid(FFA) were determined, morphological changes of myocardial tissue was observed by HE and Masson staining, mRNA and protein expressions of PPARa were measured by qRT-PCR and Western blot analysis.Results:Compared with Sham operation group, Model control group showed increased left ventricular mass index(LVMI), collagen volume fraction(CVF) and FFA level, all P <0.05, while decreased mRNA and protein expressions of PPARa, both P<0.05. Compared with Model control group, Low-dose and High-dose astragaloside groups presented reduced LVMI, CVF and FFA level, all P<0.05-0.01, while elevated mRNA and protein expressions of PPARa, both P<0.01.Conclusion:Astragaloside Ⅳ mayinhibit myocardial remodeling in pressure-overload rats, which might be via upregulating mRNA and protein expressions of PPARa, enhance myocardium FFA utilization, and therefore improve myocardial energy metabolism.更多还原