SnoN蛋白在糖尿病大鼠肾组织中的表达及其意义  

Expression and role of SnoN in kidney tissue of diabetic rats

作　　者：刘瑞霞[1] 郭兵[1] 崔龙[1] 石明隽[1] 肖瑛[1] 方开云[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：《中国病理生理杂志》2008年第6期1188-1192,共5页Chinese Journal of Pathophysiology

基　　金：贵州省科技攻关资助项目(NoD2007-4);贵州省高层次人才科研条件特助经费项目资助(NoTZJF-2007年44号);贵阳医学院研究生创新基金资助项目(NoS200709)

摘　　要：目的:动态观察核转录共抑制因子SnoN蛋白在糖尿病大鼠肾组织中的表达变化,探讨其在糖尿病肾病(DN)发病机制中的作用。方法:SD大鼠随机分为3组,分别为糖尿病2周(DM2)、4周(DM4)和8周(DM8)组,每组均设相应的正常对照,链脲佐菌素(STZ)复制糖尿病大鼠模型;免疫组织化学法检测肾组织中SnoN、TGF-β1、Smad2/3、APC的表达;Western印迹法检测肾皮质SnoN蛋白的水平;生化方法测定血糖、血肌酐及24h尿蛋白量;光镜检查肾组织的形态改变。结果:Western印迹和免疫组化检测发现DM2大鼠肾组织中SnoN的表达与正常组相比差异无显著,DM4组明显减少(P<0.01),至8周时减少为正常对照组的42%。DM2组,大鼠肾小管上皮细胞中TGF-β1、Smad2/3、APC较正常组显著增多,并随病程进展而增加(P<0.01);DM4和DM8组,SnoN蛋白表达的减少与TGF-β1、Smad2/3、APC表达增多呈显著负相关(P<0.01)。结论:糖尿病大鼠肾脏TGF-β1表达增多,可能通过APC依赖的泛素化作用使SnoN蛋白降解,从而在DN的发病机制中起重要作用。AIM： To observe the changes of SnoN expression in renal tissues of diabetic rats, and to elucidate the role of co-repressor SnoN protein in the diabetic nephropathy. METHODS. Diabetic nephropathy was induced by in-travenous injection of streptozotocin in male Sprague - Dawley rats. The model animals were divided into 2 weeks, 4 weeks and 8 weeks groups randomly. Meanwhile other 3 age-matched normal control groups were set up. The expressions of SnoN, TGF -β1, Smad2/3, APC were detected by immunohistochemistry staining. The SnoN proteins in renal cortex were detected by Western blotting. Blood glucose, serum creatinine and 24 h urine protein were examined by biochemistry methods. The renal morphology was checked on PAS staining sections under light microscopy. RESULTS ： The results of immunohistochemistry and Western blotting showed that the expression of SnoN in diabetic renal tissues at 2 weeks was the same as the normal kidney. There was a significant decrease in DM 4 weeks （P 〈0. 01 ）. A time dependent increases in TGF -β1, Smad2/3 and APC were detected in the kidney of diabetic mellitus rats. The degree of SnoN down-regulation had close relation with the increases in TGF - β1 Smad2/3 and APC. CONCLUSION： These results suggest that in the DM, renal increase in TGF -β1 expression may down-regulate the SnoN expression through APC dependent degradation, indicating a key role in the mechanism of diabetic nephropathy.

关 键 词：转录共抑制因子SnoN 转化生长因子Β 蛋白质Smad2/3 糖尿病肾病 

分 类 号：R363[医药卫生—病理学]