文献类型：期刊文献

中文题名：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

英文题名：Investigating the mechanism of astragalosideⅣin radiation-induced heart injury via the Trim32/Pink1/Parkin signaling pathway

作者：王雪含[1,2];成慧昕[1];陈其林[2,3,4];张育贵[5];支晓东[2,3];李倩蓉[2,3];李琳婵[2,3];赵信科[2,3];李应东[1,2,3]

第一作者：王雪含

机构：[1]兰州大学第一临床医学院,甘肃兰州730000;[2]甘肃省中医药防治慢性病重点实验室,甘肃兰州730000;[3]甘肃中医药大学中西医结合学院,甘肃兰州730000;[4]贵州茅台医院,贵州遵义563000;[5]甘肃中医药大学药学院,甘肃兰州730000

第一机构：兰州大学第一临床医学院,甘肃兰州730000

年份：2026

卷号：42

期号：5

起止页码：886

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：甘肃教育揭榜挂帅项目(No 2021jyjbgs-03);甘肃省中医药防治重大疾病专项(No GZKZD-2018-02);甘肃省科技重大专项(No 20ZD7FA002)。

语种：中文

中文关键词：放射性心脏病;黄芪甲苷Ⅳ;线粒体稳态;Trim32/Pink1/Parkin信号通路

外文关键词：radiation-induced heart disease;astraga?losideⅣ;mitochondrial homeostasis;Trim32/Pink1/Parkin signaling pathway

摘要：目的旨在探讨黄芪甲苷Ⅳ(astragalosideⅣ,AS-Ⅳ)是否通过调控Trim32/Pink1/Parkin信号通路,改善辐射诱导的心肌损伤,并阐明其潜在的作用机制。方法采用体外培养的H9c2心肌细胞,通过流式细胞术检测细胞凋亡与活性氧(reactive oxygen species,ROS)水平;采用荧光染色评估细胞活性与线粒体形态;利用siRNA敲低Trim32表达以验证其功能。在体内,构建放射性心脏病大鼠模型,予以AS-IV干预后,通过超声、Masson染色、HE染色、WGA染色、透射电镜观察心肌组织病理变化与超微结构;通过Western blot法检测相关蛋白表达水平。结果体外实验表明,高剂量AS-IV处理可明显降低心肌细胞凋亡率(P<0.01)与ROS水平(P<0.01),并有效改善线粒体碎片化形态。敲低Trim32可产生与AS-Ⅳ类似的抗凋亡和改善线粒体结构的保护效应。体内实验证实,AS-Ⅳ能明显改善大鼠的心功能,减轻心肌纤维化、细胞排列紊乱及肥大等病理改变,并修复线粒体嵴膜结构的断裂与肿胀。分子机制研究表明,AS-Ⅳ能下调辐射后高表达的Trim32,同时上调Pink1、Parkin表达,并逆转Bax、Bcl-2的表达。结论AS-Ⅳ能够改善辐射诱导的心肌细胞凋亡与线粒体功能障碍,机制可能与抑制Trim32表达,进而激活Pink1/Parkin信号通路有关。
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-Ⅳtreatment 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-Ⅳdown?regulated radiation-induced overexpression of Trim32,upregulated Pink1 and Parkin protein expression,and reversed the expression of Bax and Bcl-2.Conclu?sions AS-Ⅳsignificantly ameliorates radiationinduced 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.