【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。更多还原

【Abstract】 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.更多还原