高迁移率族蛋白B1通过TGF-β/Smad3信号通路降低缺氧/复氧诱导的心肌细胞纤维化的机制  

The mechanism of HMGB1 in regulating cardiomyocyte fibrosis induced by hypoxia/reoxygenation through TGF-β1/Smad3 signaling pathway

作　　者：徐敏[1] 岳峰[1] 宋勃[1] 周松[1] 黄晶[1] 田水[1] 刘启方[1] XU Min;YUE Feng;SONG Bo(Guizhou province people's hospital,Guiyang,550002)

机构地区：[1]贵州省人民医院康复科,贵州省贵阳市550002

出　　处：《中国康复医学杂志》2022年第8期1018-1022,1056,共6页Chinese Journal of Rehabilitation Medicine

基　　金：国家临床重点专科建设项目(国卫办医函[2013]544号);贵州省科技支撑计划项目(黔科合平台人才[2017]5405号);贵州省科技厅(黔科合基础-ZK[2022]一般255)。

摘　　要：目的:探讨高迁移率族蛋白B1(HMGB1)在缺氧/复氧诱导H9C2心肌细胞纤维化过程中的作用及机制。方法:构建转染HMGB1-shRNA H9C2稳定细胞系沉默HMGB1的表达,行缺氧/复氧损伤处理,Western Blot检测纤维化相关蛋白的表达,同时检测TGF-β1、ERK及Smad3纤维化信号通路相关因子,明确下调HMGB1表达对心肌纤维化蛋白及纤维化信号通路蛋白表达的影响。使用TGF-β1抑制剂SB431542与H9C2心肌细胞共培养,行缺氧/复氧损伤处理,Western Blot检测纤维化相关蛋白的表达,明确TGF-β1对心肌纤维化蛋白表达的影响。结果:转染HMGB1-shRNA的H9C2细胞,行缺氧/复氧处理,HMGB1蛋白及纤维化相关蛋白TIMP2、MMP2、CollagenⅠ和CollagenⅢ表达水平下调,与对照组相比差异具有显著性意义(P<0.05);TGF-β1、p-Smad3蛋白表达下调,与对照组相比差异具有显著性意义(P<0.05)。使用TGF-β1抑制剂SB431542,行缺氧/复氧处理,纤维化相关蛋白TIMP2、MMP2、CollagenⅠ和CollagenⅢ表达水平下调,与对照组相比,差异具有显著性意义(P<0.01)。结论:HMGB1影响缺氧/复氧诱导的H9C2心肌细胞纤维化,其作用机制可以通过下调TGFβ1/Smad3信号通路蛋白的表达降低心肌纤维化。Objective:To explore the role and mechanism of HMGB1 in regulating myocardial fibrosis induced by hypoxia/reoxygenation.Method:The cardiomyocyte H9C2 cells transfected with HMGB1-shRNA were subjected to hypoxia/reoxygenation. The expression levels of HMGB1、TGF-β1、p-ERK、p-Smad3 and the protein of myocardial fibrosis were determined by Western Blot analysis. SB431542(inhibitor of TGF-β1/Smad3) was used in cardiomyocyte H9C2cells exposed to hypoxia/reoxygenation. Western Blot was performed to examine the expression levels of TIMP2、MMP2、Collagen Ⅰ and Collagen Ⅲ.Result:Downregulated HMGB1 inhibited the expression of TGF-β1、p-Smad3、TIMP2、MMP2、Collagen Ⅰ and Collagen Ⅲ(P<0.05). SB431542 alleviated the expression levels of TIMP2、MMP2、Collagen Ⅰ and CollagenⅢ(P<0.01).Conclusion:HMGB1 regulate cardiomyocyte fibrosis via the TGF-β1/Smad3 signaling pathway in hypoxia/reoxygenation H9C2 cell.

关 键 词：高迁移率族蛋白B1 缺血/再灌注 心肌纤维化 TGF-β1/Smad3信号通路 

分 类 号：R541.4[医药卫生—心血管疾病] R493[医药卫生—内科学]