【摘要】 目的 探讨线粒体乙醛脱氢酶2(ALDH2)特异性激动剂Alda-1对高糖诱导的心肌成纤维细胞（CFs）晚期糖基化终产物-糖基化终产物受体（AGEs-RAGE）轴与基质金属蛋白酶（MMPs）通路相关蛋白基质金属蛋白9(MMP-9)/基质金属蛋白酶抑制剂1(TIMP-1)的影响及其在DM心肌纤维化中的作用及机制。方法 原代培养乳鼠CFs，随机分为正常对照组（Con）、Con+Alda-1组、高糖组（HG）、HG+Alda-1组、HG+Alda-1+ALDH2抑制剂Daidzin组（HG+Alda-1+Daidzin）及HG+Daidzin组。各组心肌成纤维细胞干预48 h后，免疫荧光观察CFs向肌成纤维细胞转化，Western blot法检测各组AGE、RAGE、MMP-9及TIMP-1蛋白表达。结果 与Con组比较，HG组CFs向肌成纤维细胞转化增加（P<0.01）,AGEs、RAGE、MMP-9及TIMP-1蛋白表达升高（P<0.05或P<0.01）。与HG组比较，HG+Alda-1组CFs向肌成纤维细胞转化减少（P<0.01）,AGEs、RAGE、MMP-9及TIMP-1蛋白表达降低（P<0.05）。与HG+Alda-1组比较，HG+Alda-1+Daidzin组CFs向肌成纤维细胞转化增加（P<0.01）,AGEs、RAGE、MMP-9及TIMP-1蛋白表达升高（P<0.01）。结论 Alda-1可能通过抑制AGEs-RAGE轴，调控MMPs蛋白家族抑制高糖引起的CFs向肌成纤维细胞转化，减轻DM心肌纤维化。更多还原

【Abstract】 Objective To investigate the effects of Alda-1,the specific agonist of acetaldehyde dehydrogenase 2(ALDH2)on the advanced glycosylation end products,(AGEs）-receptor of the advanced glycosylation end product(RAGE)axis and matrix metalloproteinases(MMPs)in high glucose-induced cardiac fibroblasts fibrosis,and explore the underlying mechanism.MethodsThe primary culture of cardiac fibroblasts(CFs)were randomly divided into 6 groups:normal group(Con),Con+Alda-1 group,high glucose group(HG),HG+Alda-1 group,HG+Alda-1+Daidzin(the inhibitor of ALDH2)group,and HG+Daidzin group.The transformation of cardiac fibroblasts into myofibroblasts was detected by the immune of luorescence double staining method after high glucose and drug intervention for 48 h.AGEs,RAGE,matrix metalloproteinase-9(MMP-9),and tissue inhibitor of metalloproteinase-1(TIMP-1)protein expressions in cardiac fibroblasts were determined by Western blotting.ResultsCompared with Con group,the transformation of CFs into myofibroblasts increased(P<0.01),and the expressions of AGEs,RAGE,MMP-9 and TIMP-1 increased(P<0.05 or P<0.01)in HG group.Compared with HG group,the transformation of CFs into myofibroblasts decreased(P<0.01),and the protein expressions of AGEs,RAGE,MMP-9 and TIMP-1 decreased(P<0.05)in HG+Alda-1 group.Compared with HG+Alda-1group,the transformation of CFs into myofibroblasts increased(P<0.01),and the expressions of AGEs,RAGE,MMP-9 and TIMP-1 proteins increased(P<0.01)in HG+Alda-1+Daidzin group.Conclusion Alda-1 alleviated the fibrosis injury of cardiac fibroblasts induced by high glucose through inhibiting the AGEs-RAGE axis and regulating the MMPs family,thus offering protection against myocardial fibrosis in diabetics.更多还原