Alda-1对高糖诱导的心肌成纤维细胞纤维化中晚期糖基化终产物-糖基化终产物受体轴及基质金属蛋白酶9/基质金属蛋白酶抑制剂1的影响  

Effects of Alda-1 on the advanced glycosylation end product-receptor of advanced glycosylation end product axis and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in high glucose-induced cardiac fibroblast fibrosis

作　　者：梁欢 黄毓慧 谷小雨 程向阳[3] 高琴[4] LIANG Huan;HUANG Yuhui;GU Xiaoyu(Bengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular diseases,Bengbu 233030,China)

机构地区：[1]蚌埠医学院心脑血管疾病基础与临床重点实验室,蚌埠233030 [2]陕西省核工业二一五医院麻醉科 [3]蚌埠医学院第一附属医院麻醉科 [4]蚌埠医学院生理学教研室

出　　处：《中国糖尿病杂志》2023年第7期528-534,共7页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81770297);蚌埠医学院研究生科研创新计划(Byycx20004)

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。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.Methods The 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.Results Compared 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-1 group,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.

关 键 词：高糖 线粒体乙醛脱氢酶2 心肌纤维化 晚期糖基化终产物-糖基化终产物受体轴 基质金属蛋白酶 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]