GLP-1减轻糖基化终末产物对肾小管上皮细胞(HK-2)重吸收功能的影响  

GLP-1 alleviates the effect of advanced glycation end products on re-absorption function of HK-2

作　　者：尹卫芹 许世清[2] 翟敏 王在[2] 娄晋宁[2] YIN Wei-qin;XU Shi-qing;ZHAI Min(Graduate School of Peking Union Medical College,Chinese Academy of Medical Sciences, Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院研究生院,北京100730 [2]中日友好医院临床医学研究所,北京100029

出　　处：《中日友好医院学报》2018年第3期159-164,F0002,共7页Journal of China-Japan Friendship Hospital

摘　　要：目的:研究GLP-1对糖基化终末产物(AGEs)引起人近端肾小管上皮细胞(HK-2细胞)损伤的影响及机制。方法:将HK-2细胞分成4组:正常对照组,AGEs处理组,AGEs+GLP-1处理组和AGEs+Insulin处理组,分别培养24h。检测各组细胞对荧光标记白蛋白的吸收能力。结果:与正常组相比,AGEs处理组细胞吸收白蛋白的能力减弱,与重吸收相关的通道蛋白Megalin和Cubilin表达降低。AGEs+GLP-1处理组细胞吸收白蛋白的能力与正常对照组相似,给予胰岛素无明显保护作用,与AGEs处理组无差别。进一步研究发现,AGEs处理组较正常对照组的PKA表达降低,PKC表达升高;同时诱导型一氧化氮合酶(iNOS)升高,超氧化物歧化酶(SOD)降低。给予GLP-1可减轻AGEs的作用。采用信号通路激活剂或阻断剂后发现,抑制PKA或激活PKC可以拮抗GLP-1对iNOS和SOD的调节作用。结论 :GLP-1可能通过调节PKA和PKC水平降低AGEs引起的肾小管上皮细胞氧化应激,从而维持通道蛋白的表达,改善细胞对白蛋白的重吸收功能。Objective：To explore the effects of GLP-1 on AGEs-induced injury of human proximal tubular epithelial（HK-2）cells and its mechanism.Methods：HK-2 cells were divided into four groups：normal group cultured in M199 medium containing 5% FCS,AGEs group cultured in medium supplied with AGEs;AGEs ＋GLP-1 group cultured in medium supplied with both AGEs and GLP-1;and AGEs＋Insulin group cultured in medium supplied with both AGEs and Insulin.Albumin absorbabiligy of HK-2 cells was detected by measuring the fluorescence intensity.Results：Compared with normal group,the absorption of albumin was decreased in AGEs group,and megalin as well as cubilin were also down-regulated.In AGEs ＋GLP-1 group,the albumin absorption,megalin and cubilin level were similar to normal group.However,there were no difference between AGEs＋Insulin group and AGEs group.Compared with normal group,AGEs treatment down-regulating PKA and up-regulating PKC,accompanied with high iNOS and low SOD levels.This indicated oxidative stress occurred.Treated with GLP-1 but not insulin could inhibit the effect of AGEs.But the action of GLP-1 on the expression of iNOS and SOD could be blocked by PKA inhibitor or PKC activator.Conclusion：GLP-1 might alleviate oxidative stress on renal tubular epithelial cells by regulating PKA/PKC,which maintained the expression of megalin and cubilin,then improved the re-absorption function of renal tubular epithelial cells

关 键 词：胰高糖素样肽1 糖基化终末产物 肾小管上皮细胞 氧化应激 蛋白激酶C 蛋白激酶A 

分 类 号：R363.2[医药卫生—病理学]