糖尿病大鼠肾组织内Smads信号通路活化的动态观察

Activation of Smads signal pathway in kidney of STZ-induced diabetic nephropathy rats

目的动态观察大鼠糖尿病肾病发生发展过程中TGF-β1的下游信号分子正负反馈调节因子Smad2及其活化形式Psmad2在肾脏的表达变化。方法 40只SD大鼠随机分成4组:正常对照组、4周组、8周组和16周组。链脲菌素(STZ)诱导糖尿病肾病模型,动态观察各组大鼠血压,24h尿量,ELISA测尿液浓度从而行24h尿白蛋白定量、肾重/体重、血肌酐和肾脏病理。免疫组化、Western blotting方法动态观察糖尿病大鼠肾病发生发展过程中肾组织内Smad2和Psmad2蛋白表达。结果 Smad2蛋白4周表达比正常增多,但差异无统计学意义(P>0.05),从8周起表达明显多于正常组(P<0.05),Psmad2蛋白从4周开始即比正常组表达增多(P<0.05),且随着糖尿病进展逐渐增加。结论 Smad2信号转导通路参与了糖尿病肾病肾脏纤维化过程,早期Smad2信号蛋白活化较明显,继而Smad2蛋白也表达增加,再刺激Smad2活化增多,形成的放大效应是导致糖尿病肾病肾脏纤维化进展重要的信号转导途径之一。

ObjectiveTo study the role of positive feedback factor Smad2 and its activated form Psmad2 in TGF-β/Smad pathway during the development of renal fibrosis in diabetic nephropathy.MethodsThirty SpragueDawley rats injected with streptozotocin（STZ） were randomly divided into 4W,8W,16W groups,other ten normal rats were used as controls.The systolic blood pressure,serum creatinine,24 hours urine volume,ratio of KW（kidney weight） to BW（body weight） were measured.ELISA was used to quantify 24 h urine protein.Renal injury was also assessed by kidney pathology.The expression of Smad2 and Psmad2 were detected by immunohistochemical method and Western blotting.ResultsThere was no statistical difference in Smad2 between 4W group and normal group（P〈0.05） but a significant difference was found with control group from the 8th week on（P〈0.05）.Psmad2 increased from the 4th week on compared with control group（P〈0.05）.There was an increasing tendency in both proteins with the passage of time（P〈0.05）.ConclusionsThe results indicate that Smad2 pathway is involved in pathophysiological process of diabetic nephropathy.It may be one of the important pathways in diabetic renal fibrosis through activation of Smad2,upregulation of Smad2 expression,activation of Smad2 again.