【摘要】 目的探讨黄芪注射液(Astragalus injection,AS)对大鼠心肌梗死后心肌重塑的逆转作用及其作用机制。方法通过结扎左冠状动脉前降支建立大鼠心肌梗死后心肌重塑模型,实验分为假手术组、模型组、AS低剂量组(1 m L/kg)及高剂量组(3 m L/kg)。研究AS治疗6周对其生存百分率、血清中α肌球蛋白重链(α-MHC)和大鼠N端前脑钠素(NT-PROBNP)的影响;同时HE染色及Masson染色以检测心脏组织病理学变化及其心肌纤维化情况; ELISA法检测各组血清中MDA、NO及e NOS的变化; Western blotting法检测心肌细胞PI3K、P-AKT、及Pe NOS蛋白的表达。结果 AS高低剂量组与模型组比较,生存百分率有所提高,但无显著性差异;而AS高剂量组α-MHC及NT-PROBNP较模型组显著降低(P<0. 05); HE及Masson染色形态学检查显示,与模型组比较,AS高剂量组炎细胞浸润、出血及纤维化程度减轻;高剂量组血清中MDA降低(P<0. 001)、NO及e NOS的升高(P<0. 05); Western blot结果显示,AS组的PI3K、p-AKT表达量高于模型组(P<0. 05),p-eNOS表达亦显著上升。结论黄芪注射液可能通过激活PI3K/AKT通路降低氧化应激水平,从而抑制心肌梗死后心肌重塑。更多还原

【Abstract】 Objective To examine the effect of Astragalus( AS) injection on post-myocardial infarction-induced cardiac remodeling in rats,and explore potential mechanisms underlying such effects. Methods A cardiac remodeling post-myocardial infarction model was prepared in rats,which were divided into four groups: sham operation,myocardial infarction( model group),low-dose AS( ASL,1 m L/kg),and high-dose AS( ASH,3 m L/kg). Survival rate of the rats and activities of the alpha isoform of myosin heavy chain( α-MHC) and N-terminal pro b-type natriuretic peptide( NTpro BNP) in rat serum were measured after 6-week treatment. Histopathological changes and myocardial fibrosis were observed by light microscopy using hematoxylin and eosin,and Masson trichome staining. Quantification of malondialdehyde( MDA),nitric oxide( NO),and endothelial nitric oxide synthase( e NOS) were carried out using enzyme-linked immunosorbent assays. Protein expression of phosphatidylinositol 3 kinase( PI3 K),phosphorylated AKT( p-AKT),and pe NOS were analyzed by western blotting. Results Compared with the model group,the survival rate of the ASL and ASH group were increased,but not significantly( P > 0. 05). Meanwhile,α-MHC and NT-proBNP contents in the ASH group were reduced( P < 0. 05). In addition,inflammation,hyperemia,and interstitial fibrosis were reduced in the ASH group.Moreover,the ASH group exhibited increased protein expression of PI3 K and p-AKT in the injured heart( P < 0. 05). pe NOS expression in the ASH group was increased compared with the model group( P < 0. 05). Conclusions AS elicits an obvious protective effect on cardiac remodeling after myocardial infarction in rats. Activation of the PI3 K/AKT pathway may activate p-eNOS,which is involved in the mechanism by which AS prevents oxidative stress during cardiac remodeling.更多还原