基于Trim32/Pink1/Parkin信号通路探讨黄芪甲苷Ⅳ对放射性心肌损伤的作用机制OA

Aim To investigate whether astragalosideⅣ(AS-Ⅳ)ameliorates radiation-induced heart dis-ease(RIHD)by regulating the Trim32/Pink1/Parkin signaling pathway and to elucidate its underlying mechanism.Methods In vitro cultured H9c2 cardio-myocytes were used.Apoptosis and ROS levels were detected by flow cytometry.Cell viability and mito-chondrial morphology were assessed using fluorescent staining.Trim32 expression was knocked down with siRNA to validate its function.For in vivo studies,a rat model of RIHD was established and treated with AS-Ⅳ.The pathological changes and ultrastructure of myocardial tissue were observed by ultrasound,Mas-son,HE,WGA and transmission electron micros-copy.Protein expression levels were detected using Western blotting.Results In vitro experiments dem-onstrated that high-dose AS-Ⅳ treatment significantly reduced cardiomyocyte apoptosis(P<0.01)and ROS levels(P<0.01),and effectively ameliorated mito-chondrial fragmentation.Knockdown of Trim32 pro-duced protective effects similar to those of AS-Ⅳ,in-cluding anti-apoptosis and improved mitochondrial structure.In vivo experiments confirmed that AS-Ⅳsignificantly improved cardiac function in rats,allevi-ated pathological changes such as myocardial fibrosis,disordered cell arrangement,and hypertrophy,and re-paired mitochondrial cristae rupture and swelling.Mo-lecular mechanism studies revealed that AS-Ⅳ down-regulated radiation-induced overexpression of Trim32,upregulated Pink1 and Parkin protein expression,and reversed the expression of Bax and Bcl-2.Conclu-sions AS-Ⅳ significantly ameliorates radiation-induced cardiomyocyte apoptosis and mitochondrial dysfunction.Its protective mechanism may be associ-ated with the inhibition of Trim32 expression,subse-quent activation of the Pink1/Parkin pathway.