中国药理学通报2026，Vol.42Issue(5)：886-896,11.DOI:10.12360/CPB202509056
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
Investigating the mechanism of astragaloside Ⅳ in radiation-induced heart injury via the Trim32/Pink1/Parkin signaling pathway
摘要
Abstract
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.关键词
放射性心脏病/黄芪甲苷Ⅳ/线粒体稳态/Trim32/Pink1/Parkin信号通路Key words
radiation-induced heart disease/astraga-loside Ⅳ/mitochondrial homeostasis/Trim32/Pink1/Parkin signaling pathway分类
医药卫生引用本文复制引用
王雪含,成慧昕,陈其林,张育贵,支晓东,李倩蓉,李琳婵,赵信科,李应东..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[J].中国药理学通报,2026,42(5):886-896,11.基金项目
甘肃教育揭榜挂帅项目(No 2021jyjbgs-03) （No 2021jyjbgs-03）
甘肃省中医药防治重大疾病专项(No GZKZD-2018-02) （No GZKZD-2018-02）
甘肃省科技重大专项(No 20ZD7FA002) （No 20ZD7FA002）
