E3泛素连接酶APC对糖尿病大鼠肾组织SnoN蛋白表达的影响

Effects of E3 Ubiquitin Ligase APC on Expression of SnoN in Renal Tissue of Diabetic Rats

目的:观察APC10在糖尿病大鼠肾组织中的表达变化,并初步探讨其与糖尿病肾病(DN)发生发展中SnoN蛋白表达变化的关系。方法:大鼠随机分为糖尿病2、4和8周组,每组均设鼠龄匹配的正常对照组;生化方法测血糖、血肌酐和24 h尿蛋白,并观察肾脏指数;免疫组织化学检测APC10、核转录共抑制因子SnoN(SnoN)、转化生长因子-β1(TGF-β1)、Smad2/3及链脲佐菌素(FN)蛋白的表达变化;RT-PCR检测SnoNmRNA的表达。结果:APC10阳性染色见于各组大鼠肾小管,随DN病程进展其表达逐渐增多,SnoN蛋白表达逐渐减少,TGF-β1、Smad2/3及FN蛋白亦随DN发展而增多;各时点糖尿病大鼠SnoN mRNA的表达与正常对照组相比差异无统计学意义。结论:APC10在DN发生发展中的表达增多可能介导了SnoN蛋白的泛素化降解,可能是SnoN蛋白表达减少的主要机制之一。

Objective： To explore the expression of anapbase promoting eomplax （APC） in renal tissues of diabetic rats, and to investigate its contribution to the change of Ski-related protein N （SnoN） in diabetic nephropathy （DN）. Methods： Diabetic nephropathy was induced by streptozotoein in male Sprague-Dawley rats, and then these rats were randomly divided into 3 groups with disease courses of 2 weeks,4 weeks, and 8 weeks respectively. Three age-matched normal control groups were set up simultaneously. Blood glucose （BG）, Serum creatinine （Scr）, and 24 h urine protein （UP） were detected with biochemistry method, and kidney index was measured. Expression of APC10, SnoN, TGF- β1 Smad2/3 and FN protein were detected by immunohistochemistry method, and SnoN mRNA was detected by RT-PCR. Results： APCIO protein positive staining was observed in renal tubules of all groups, and APCIO expression was significantly up-regulated in renal cortex of diabetic rats （P 〈 0. 05） . SnoN protein tapered in diabetic renal tissues. There was a time dependent increase of TGF- β1, Smad2/3 and FN in the kidney of DN rats. No significant difference of SnoN mRNA was detected in rats between control group and DN group. Conclusion： The increases of APC10 expression during the development of DN may leads to ubiquitin mediated degradation of SnoN protein, which might be one of the main causes for the decrease of SnoN protein.