中文摘要：

目的观察Sirt1激活剂SRT1720对高糖诱导的小鼠肾小球系膜细胞凋亡的作用。方法体外培养小鼠肾小球系膜细胞,随机分为正常糖组、正常糖＋甘露醇组、高糖组及高糖＋SRT1720组。采用原位末端转移酶标记技术（TUNEL）及流式细胞术检测细胞凋亡;流式细胞术检测活性氧簇（ROS）产生;Western blot检测caspase-3、cleaved caspase-3、Bax、Bcl-2、p38 MAPK、p-p38 MAPK、Sirt1、p53、乙酰化p53及细胞色素C的表达;实时定量PCR检测Bax和Bcl-2 mRNA的表达。结果与正常糖对照组相比,高糖组系膜细胞ROS产生和细胞凋亡明显增加,cleaved caspase-3、p-p38 MAPK和乙酰化p53表达增高、Bax/Bcl-2比率明显升高、Sirt1表达下降以及细胞色素C易位。SRT1720干预能够明显抑制高糖诱导的系膜细胞凋亡和ROS产生;下调cleaved caspase-3、乙酰化p53和p-p38 MAPK的表达;上调Sirt1的表达;减少Bax/Bcl-2比率和细胞色素C易位。结论SRT1720能够抑制高糖诱导的系膜细胞凋亡,可能是通过减少ROS产生、保护线粒体功能、抑制p53乙酰化以及p38MAPK信号通路激活而实现的。

英文摘要：

Aim To investigate the effect of Sirt1 activator SRT1720 on high glucose（ HG）-induced apoptosis in mouse mesangial cells（ MMCs）. Methods Cultured mouse MMCs were divided into normal glucose group（ NG）,NG plus mannitol group（ M）,high glucose group（ HG）,HG plus SRT1720 group（ HG ＋SRT）. Apoptosis of MMCs was analyzed by DeadEndTMFluorometric TUNEL System and flow cytometry. Reactive oxygen species（ ROS） production was observed by flow cytometry. The expression levels of caspase-3, cleaved caspase-3, Bax, Bcl-2, p38 MAPK,p-p38 MAPK,p53,acetylated p53 and cytochrome C protein were observed by Western blot. The mRNA levels of Bax and Bcl-2 were detected by realtime PCR. Results Compared with normal glucose group,the production of ROS,the number of cell apoptosis,the expression of cleaved caspase-3,p-p38 MAPK and acetylated p53 and ratio of Bax/Bcl-2 were significantly increased,the expression of Sirt1 was decreased,meanwhile,the release of cytochrome C from mitochondria to cytoplasm was significantly increased in MMCs in high glucose group. Treatment with SRT1720 inhibited HG-induced increase of ROS production,cell apoptosis,expression of cleaved caspase-3,acetylated p53 and p-p38 MAPK,ratio of Bax/Bcl-2 and release of cytochrome C,and reversed HG-induced Sirt1 expression. Conclusion SRT1720 could prevent HG-induced apoptosis maybe by decreasing ROS production,preserving mitochondrial function and inhibiting p53 acetylation and activation of p38 MAPK in MMCs.