胰升血糖素样肽-1减轻晚期氧化蛋白产物所致足细胞氧化应激损伤的实验观察  

Experimental observation of glucagon-like peptide-1 attenuating oxidative stress injury of podocytes induced by advanced oxidative protein products

作　　者：张双双[1] 张振[1] 杨蕾[1] 罗惠金 陈宏[1] 

机构地区：[1]南方医科大学珠江医院内分泌科,广州510280

出　　处：《中国糖尿病杂志》2016年第11期1007-1011,共5页Chinese Journal of Diabetes

基　　金：广东省省级科技计划项目(2013B021800315);广东省药学会科学研究基金(2013X07)

摘　　要：目的探讨胰升血糖素样肽-1(GLP-1)对晚期氧化蛋白产物(AOPPs)诱导足细胞损伤的影响。方法以小鼠永生性足细胞系为研究对象,分为对照(Con)组、AOPPs组、GLP-1组、AOPPs+GIP-1组,CCK8试剂盒检测足细胞增殖活性,DHE荧光探针检测细胞内活性氧簇(ROS)水平,光泽精化学发光法测定还原型辅酶II(NADPH)氧化酶的活性,酶标仪法检测SOD活性、MDA及还原型谷胱甘肽(GSH)含量;Western blot检测足细胞特异性标志蛋白podocin、nephrin的表达情况。结果 GLP-1可呈浓度依赖性地拮抗AOPPs诱导的足细胞增殖活性降低,减少ROS产生[荧光强度为(48.93±2.99)],降低NADPH氧化酶活性(较AOPPs组下降40.1%);增加SOD酶活性和GSH含量,减少MDA产生,并增加nephrin、podocin蛋白表达(P<0.05,分别为AOPPs组的1.29倍、1.44倍)。结论 GLP-1能减轻AOPPs诱导的足细胞损伤,可能与抑制NADPH氧化酶介导的氧化应激有关。Objective To investigate the effect of glucagon-like peptide-1 （GLP-1） on podocytes injury induced by advanced oxidative protein products （AOPPs）. Methods Murine podocytes were selected and divided into four groups： control group, AOPPs group, GLP-1 group and AOPPs＋ GLP-1 group. Cell viability was detected by CCK-8 assay. Reactive oxygen species （ROS） level and NADPH oxidase activity were tested by DCFH-DA staining and lucigenin-enhanced chemiluminescence assay respectively. Superoxide dismutase （SOD） viability, malondialdehyde （MDA） and glutathione （GSH） content were determined by ELIS/L The expression of podocin and nephrin protein were evaluated by western blot. Results GLP-1 increased cell viability in a dose-dependent manner induced by AOPPs. The DHE-sensitive ROS generation was significantly lower in AOPPs ＋ GLP-1 group than in AOPPs group （48. 93 ±2.99）, as well as the NADPH oxidase activity （decreased by 40. 1%） （P〈0. 05）. Exposure to GLP-1 caused a significant increase in SOD viability and GSH content, and a remarkable decrease in the level of MDA （P〈0. 05）. GLP-1 also enhanced the expression of podocin and nephrin by 1.29 and 1.44 fold respectively compared to AOPPs group （P〈0.05）. Conclusion GLP-1 prevents podocytes injury induced by AOPPs. The mechanism may be related to the inhibition of NADPH oxidase- mediated oxidative stress.

关 键 词：胰升血糖素样肽-1 足细胞 晚期氧化蛋白产物 氧化应激 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]