抗氧化肽SS-31对高糖诱导的小鼠肾小球系膜细胞凋亡的影响  

Influence of antioxidant peptide SS-31 on HG-induced mouse mesangial cells apoptosis

作　　者：王月华[1] 侯延娟[1] 任韫卓[1] 韦金英[1] 杜春阳[1] 张连珊[1] 史永红[1] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017

出　　处：《中国药理学通报》2013年第1期102-107,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81170673;81270804);高等学校博士学科点专项科研基金资助项目(No20091323120001);河北省自然科学基金资助项目(NoC2011206147)

摘　　要：目的观察抗氧化肽SS-31对高糖诱导小鼠肾小球系膜细胞凋亡的影响。方法将体外培养小鼠肾小球系膜细胞分为正常糖组、正常糖+甘露醇组、高糖组及高糖+SS-31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;流式细胞术检测细胞ROS水平;Western blot检测caspase-3、cleaved caspase-3、Bax、Bcl-2、p38 MAPK、p-p38 MAPK及细胞色素C的表达。结果与正常糖组相比,高糖组系膜细胞ROS产生和细胞凋亡明显增加,cleavedcaspase-3和p-p38 MAPK表达增高,Bax/Bcl-2比率明显升高以及细胞色素C易位。SS-31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和p-p38 MAPK的表达,减少Bax/Bcl-2比率和细胞色素C易位。结论 SS-31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p38MAPK信号通路激活而实现的。Aim To investigate the effect of antioxi- dant peptide SS-31 on high glucose （HG）-induced ap- optosis in mouse mesangial cells （MMCs）. Methods Cultured MMCs were divided into normal glucose group（ NG）, NG plus mannitol group （ M）, high glu- cose group （HG） and HG plus SS-31 group （ HG ＋ SS- 31 ）. Apoptosis of MMCs was analyzed by Dead End Fluorometric TUNEL System and flow cytometry. ROS production was observed by flow cytometry. The ex- pression levels of caspase-3, cleaved caspase-3, Bax, Bcl-2, p38 MAPK, p-p38 MAPK and cytochrome c protein were observed by Western blot. Results Com- pared with normal glucose group （NG）, the production of ROS, the number of cell apoptosis, the expressionof cleaved caspase-3 and Bel-2 and the release of p-p38 MAPK, ratio of Bax/ cytochrome c from mitochon- dria to cytoplasm significantly increased in MMCs in high glucose group （HG）. Treatment with SS-31 in- hibited HG-induced ROS production, cell apoptosis, expression of cleaved caspase-3 and p-p38 MAPK, ra- tio of Bax/Bcl-2 and release of cytochrome c from mito- chondria to cytoplasm in MMCs. Conclusions SS-31 can prevent HG-induced MMC apoptosis through de- creasing ROS production, preserving mitochondrial function and inhibiting activation of D38 MAPK.

关 键 词：糖尿病肾病 氧化应激 小鼠肾小球系膜细胞 SS-31 肽 凋亡 线粒体 

分 类 号：R-332[医药卫生] R322.61