摘要
目的:观察锌指转录因子Snail1在糖尿病大鼠肾组织中的表达并探讨其与糖尿病肾病(DN)发生、发展的关系。方法:链脲佐菌素(STZ)诱发大鼠糖尿病(DM),分为2、4、8、12、16、20、24周以及16周A、20周A和24周A组,其中A组动物从第13周起用胰岛素控制血糖至正常水平,每个时点均设鼠龄匹配的正常对照组。测定各组血糖、24h尿蛋白、血肌酐(Scr)、肾脏指数。PAS染色光镜观察肾脏病理改变。免疫组化、RT-PCR方法检测肾皮质Snail1和纤连蛋白(FN)的蛋白及mRNA水平,Western blotting检测Snail1蛋白表达。结果:DM各组大鼠的血糖、24h尿蛋白、血肌酐、肾脏指数明显高于正常对照组(P<0.05,P<0.01),A组上述指标均明显低于DM组(P<0.05,P<0.01)。Snail1免疫组化阳性染色见于各组DM大鼠肾小管,正常对照组未见阳性表达,A组见弱阳性表达,并随治疗时间延长而减少。DM组肾皮质Snail1、FN蛋白和mRNA的表达水平高于正常对照组(P<0.01),而A组显著低于DM组(P<0.01)。Snail1与FN mRNA的表达水平呈显著正相关(P<0.01),Snail1蛋白表达水平与血糖、尿蛋白、血肌酐、肾脏指数亦呈正相关(P<0.01)。结论:Snail1基因和蛋白在DM大鼠肾组织过度表达,提示Snail1可能参与了DN的发生、发展机制。
AIM： To explore the expression of Snail 1 in renal tissues of diabetic rats, and to investigate its contribution to the progression of diabetic nephropathy. METHODS ： Streptozotocin - induced diabetic rats were randomly divided into 2, 4, 8, 12, 16, 20, 24 weeks groups and 16 week A, 20 week A and 24 week A groups. A groups were treated with insulin to control blood glucose to normal level from the 13th week. Control groups were set up in age - matched time points. Blood glucose, 24 h urine protein, serum creatinine （Scr） and kidney index of rats were measured. Periodic acid- silver （PAS） staining was used to observe the renal pathological changes. The mRNA and protein expres- sions of Snail 1 and FN in renal cortex were detected by RT - PCR and immunohistochemical staining, respectively. Western blotting was employed to detect the expression of Snail 1 protein in the renal cortex. RESULTS： The levels of blood glucose, Scr, kidney weight index were increased remarkably in diabetic rats as compared with those in control groups （P 〈0. 05, P 〈0. 01 ）, and decreased remarkably in the insulin- treated rats as compared with those in the diabetic rats （P 〈 0. 05, P 〈 0. 01 ）. The Snail 1 protein was not detected by immunohistochemical staining in normal renal tissues. However, strongly positive staining was observed in renal tubules of diabetic rats. A time - dependent loss of Snail 1 expression was detected in the kidney in insulin - treated rats. The Snail 1 protein and mRNA of Snail 1 and FN were significantly up - regulated in the diabetic rats as compared with those in controls （P 〈 0.01 ）, while down - regulated in the insulin - treated diabetic rats （P 〈 0. 01 ）. A close positive relationship existed between the mRNA expression of Snail 1 and FN （r =0. 800, P 〈0. 01 ）. The level of Snail 1 protein expression was positively correlated with blood glucose, urine protein, Scr, kidney index （r =0. 877, 0. 694, 0. 522, 0. 875, P 〈0. 01 ）. CONCLUSION： These finding
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第4期737-742,共6页
Chinese Journal of Pathophysiology
基金
贵州省高层次人才特助经费资助项目(No2004-0517)
贵州省省长基金资助项目(No2005-303)
