黄芪注射液调节PI3K/AKT通路改善心肌梗死后心肌重塑

Protective effect of astragalus injection in cardiac remodeling after acute myocardial infarction via PI3K/AKT pathway activation

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 mL/kg)及高剂量组(3 mL/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eNOS的变化;Western blotting法检测心肌细胞PI3K、P-AKT、及P-eNOS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eNOS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。

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 mL/kg),and high-dose AS(ASH,3 mL/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(NT-proBNP)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(eNOS)were carried out using enzyme-linked immunosorbent assays.Protein expression of phosphatidylinositol 3 kinase(PI3K),phosphorylated AKT(p-AKT),and p-eNOS 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 PI3K and p-AKT in the injured heart(P<0.05).p-eNOS 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 PI3K/AKT pathway may activate p-eNOS,which is involved in the mechanism by which AS prevents oxidative stress during cardiac remodeling.