SnoN和Smad2/3信号蛋白与糖尿病大鼠肾小管-间质纤维化的关系  

Relationship between SnoN,Smad2/3 signaling protein and fibrosis of renal tubule-interstitium in rats with diabetes

作　　者：刘瑞霞[1] 郭兵[1] 肖瑛[1] 石明隽[1] 王圆圆[1] 李晓颖[1] 张国忠[1] 

机构地区：[1]贵阳医学院病理生理学教研室,贵州贵阳550004

出　　处：《基础医学与临床》2010年第9期944-951,共8页Basic and Clinical Medicine

基　　金：贵州省科技攻关项目(黔科字S20071033号);贵州省高层次人才科研条件特助经费(TZJF-2007年-44号);贵州省科技基金(黔科合J字20082167号);贵阳医学院2009年研究生教育创新基地专项经费(B200903)

摘　　要：目的观察核转录共抑制因子SnoN和Smad2/3信号蛋白在糖尿病(DM)大鼠肾组织中的动态表达,并初步探讨它们与糖尿病肾病(DN)肾小管-间质纤维化的关系。方法尾静脉注射链脲佐菌素(STZ)复制DM大鼠模型,随机分为DM2、4、8、12、16和24周组,每组均设鼠龄匹配的正常对照组(n=6)。免疫组化及Western blot法检测肾组织SnoN、转化生长因子β1(TGF-β1)、Smad2/3、α-平滑肌肌动蛋白(α-SMA)、纤连蛋白(FN)的蛋白表达;RT-PCR检测SnoN的mRNA;生化方法测血糖、血肌酐及24 h尿蛋白量。结果DM4周起,肾组织中SnoN蛋白表达明显减少(P<0.01),DM各组SnoN的mRNA表达无变化;TGF-β1、Smad2/3及FN的蛋白表达随DM病程进展逐渐增多;DM12周始,肾小管上皮细胞可见α-SMA阳性表达。结论SnoN蛋白表达减少与TGF-β1/Smad信号通路共同参与了DN的发生发展过程。Objective To explore the expression of transcription co-repressor Ski-related protein N（SnoN） and Smad2/3 in renal tissues of diabetic rats,and to investigate their contribution to the fibrosis of renal tubule-interstitium in diabetic rats.Methods The rat model was induced by vena caudalis injection of streptozotocin（STZ）.Rats were killed at 2,4,8,12,16 and 24 week of experiments.Meanwhile,the rats were in age-matched as normal control（n=6）.The protein or mRNA level of SnoN,TGF-β1,Smad2/3,α-SMA and fibronectin（FN） in renal tissues were detected.Blood glucose,serum creatinine and 24 h urine protein were examined by biochemistry methods.Results The renal SnoN protein level was significant decreased from DM 4 weeks（P0.01）.However,SnoN mRNA level was unchanged in each diabetes group,The protein level of TGF-β1,Smad2/3 and FN was significantly up-regulated in diabetes rats.Conclusion SnoN and TGF-β1/Smad signaling pathway may play a key role in the pathogenesis of diabetic nephropathy.

关 键 词：SNON TGF-Β1 SMAD2/3 糖尿病肾病 大鼠 

分 类 号：R587.2[医药卫生—内分泌]