硫化氢对高糖诱导的小鼠足突细胞损伤的影响  

Effects of hydrogen sulfide on high glucose-induced injury of mouse glomerular podocytes

作　　者：刘晔[1] 彭力[2] 卢圣霞 杜月娟[4] 刘元涛[2] 傅余芹[1] 

机构地区：[1]山东大学第二医院肾脏内科,山东济南250033 [2]山东大学第二医院内分泌科,山东济南250033 [3]山东电力中心医院内科,山东济南250002 [4]济南市中心医院肾脏内科,山东济南250013

出　　处：《中国病理生理杂志》2014年第4期670-674,共5页Chinese Journal of Pathophysiology

基　　金：山东省自然科学基金资助项目(No.Y2006C36)

摘　　要：目的:观察硫化氢对高糖诱导的小鼠足突细胞损伤的影响并探讨其作用机制。方法:将体外培养的小鼠足突细胞系MPC5分为高糖组、正常糖组、正常糖+DL-炔丙基甘氨酸(PPG)组和高糖+NaHS组。处理后,用Western blotting检测各组细胞胱硫醚γ-裂解酶(CSE)、紧密连接蛋白2(ZO-2)、裂孔蛋白(nephrin)及β-连环蛋白(β-catenin)蛋白水平表达差异。结果:(1)高糖显著降低CSE、nephrin和ZO-2表达(P<0.05),而β-catenin的水平明显增高(P<0.05),4种蛋白变化均表现出时间依赖性;(2)正常糖培养加不同浓度PPG可显著抑制ZO-2和nephrin的表达(P<0.05),显著提高β-catenin的水平(P<0.05),3种蛋白变化呈浓度依赖性;(3)高糖诱导的足突细胞加NaHS培养后,ZO-2和nephrin表达可部分恢复(P<0.01),β-catenin表达可被部分抑制(P<0.01)。结论:本研究结果提示高糖诱导的足突细胞CSE表达降低可能是足突细胞损伤的重要机制之一。而外源性硫化氢对高糖诱导的足突细胞损伤具有一定保护作用,其机制可能与增加ZO-2表达、抑制Wnt/β-catenin通路有关。AIM： To investigate the effect of hydrogen sulfide （H2S） on high glucose （HG）-induced injury of the mouse podocyte cell line MPCS. METHODS： The cultured MPC5 cells were randomly divided into 4 groups： HG group, normal glucose （NG） group, NG ＋ DL-propargylglycine （PPG） group, and HG ＋NariS group. After treated for a certain time, the cells were collected for further detection. The expression of zonula occludens-2 （ZOo2）, nephrin, B-cate- nin and cystathionine y-lyase （CSE） was determined by Western blotting. RESULTS： High glucose significantly reduced the expression of nephrin, ZO-2 and CSE （ P 〈 0.05 ）, while the level of 13-catenin was elevated obviously （ P 〈 0.05）, all in a time-dependent manner. NG ＋ PPG inhibited the levels of ZO-2 and nephrin significantly （P 〈 0.05 ）, and increased the level of 13-catenin （P 〈 0.05 ）, all in a PPG concentration-dependent manner. HG ＋ Naris induced a more significant increase in the levels of ZO-2 and nephrin as compared with HG group （ P 〈 0.01 ）, whereas a severe reduction of B-cate- nin in HG ＋ NariS group was observed as compared with HG group. Compared with NG group, the expression of ZO-2 and nephrin was decreased obviously, and the level of 13-catenin was increased in HG ＋ Naris group. CONCLUSION： Down- regulation of CSE contributes to hyperglycemia-induced podocyte injury. Exogenous H2S protects against hyperglycemia-in- duced podocyte injury, possibly through up-regulation of ZO-2 and subsequent suppression of Wnt/B-catenin pathway.

关 键 词：糖尿病肾病 硫化氢 足细胞 胱硫醚y-裂解酶 紧密连接蛋白2 B-连环蛋白 

分 类 号：R587.1[医药卫生—内分泌]