ERK1/2对高糖环境下足细胞凋亡的作用及来氟米特对其的影响  

Effects of ERK1/2 and Leflunomide Intervention in Podocyte Apoptosis Induced by High Glucose

作　　者：史日东[1] 于为民[1] 李荣山[1] 吕欣[1] 苑玉聪[1] 

机构地区：[1]山西医科大学第二医院肾内科山西省肾脏病研究所,太原030001

出　　处：《中国中西医结合肾病杂志》2011年第5期397-399,共3页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山西省卫生厅科技攻关项目(No.20100311098-3)

摘　　要：目的:观察ERK1/2对高糖环境下足细胞凋亡的作用及来氟米特对其的影响。方法:培养的人足细胞分为正常糖组、高渗对照组、高糖组,高糖组按不同刺激时间又分为0.5h、1h、6h、12h、24h5组,应用Western印迹分析法检测各组足细胞ERK1/2信号途径中ERK1/2蛋白活化的变化。足细胞凋亡检测:将足细胞分为高糖对照组、抑制剂组、抑制剂+来氟米特(A771726)组、A771726组,将以上各组足细胞培养24h后,分别进行ERK1/2信号途径的检测同前及流式细胞仪检测足细胞的凋亡率。结果:高糖组30min可以活化ERK1/2蛋白,6h开始达高峰,持续活化到24h开始降至基础水平。正常糖及高渗对照组未能活化ERK1/2。与高糖组相比,ERK1/2蛋白抑制剂(PD98059)抑制了ERK1/2的磷酸化,使磷酸化的ERK1/2(P-ERK1/2)蛋白表达明显减少(P<0.01),从而影响了下游多种核转录因子的活化,影响目的基因的表达而增加了足细胞的凋亡(P<0.01)。A771726可以增加P-ERK1/2的表达量(P<0.01),从而减少足细胞的凋亡(P<0.05)。而PD98059可以影响A771726的作用,使其对足细胞的保护作用减弱,其凋亡率比高糖组明显增加(P<0.01)。结论:ERK1/2信号途径参与了来氟米特对足细胞的保护作用。Objective：To investigate the effects of ERK1/2 and leflunomide intervention in podocyte induced by high glucose and relevant mechanisms.Methods：Human podocytes cultured in vitro were divided into normal glucose group,high permeability group,high glucose group which was detected at 0.5 h、1 h、6 h、12 h、24 h after induced.Changes of ERK1/2 signal pathway in each group were detected by using Western blotting.Detection of podocyte apoptosis：minutes,reached the peak at hour 6;maintained the activation to hour 24,and than declined to the basal level.However,activation of ERK1 /2 was not detected in normal glucose and high podocytes were divided into high glucose control group、inhibitor group,inhibitor＋ A771726 group,and A771726 group.Changes of ERK1/2 signal pathway and podocyte apoptosis in each group were detected by using Western blotting and flow cytometry respectively after cultured for 24 hours.Results：High glucose medium induced phosphorylation of ERK1/2 as early as 30 permeability groups.Compared with high glucose group,phosphorylation of ERK1/2 was blocked by PD98059,a specific ERK1/2 activation inhibitior,which attenuated the high glucose-induced expression of P-ERK1/2 obviously（P0.01）and result to more podocyte apoptosis by influencing the activation of many downstream nuclear transcription factors and expression of target gene（P0.01）.A771726 reduced podocyte apoptosis（P0.05）by increasing expression of P-ERK1/2（P0.01）.However,PD98059 influencd the protection of A771726 to podocytes and result to more apoptosis compared with high glucose group（P0.01）.Conclusion：ERK1/2 signal pathway takes part in the protection of Leflunomide to podocytes.

关 键 词：糖尿病肾病 ERK1/2 来氟米特 A771726 足细胞 

分 类 号：R587.2[医药卫生—内分泌]