SnoN蛋白在糖尿病大鼠肾组织中的表达及其意义

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24 h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。

Expression and role of SnoN in kidney tissue of diabetic rats

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 intravenous 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.