TGF-β/Smad信号通路在肾小球硬化模型中表达的意义

Expression of TGF-β/Smad Signaling Pathway and Its Significance in Glomerulosclerosis Model

目的：通过观察在肾小球硬化动物模型中TGF-β、Smad2和Smad7蛋白和mRNA表达的意义,了解TGF-β/Smads信号通路在肾小球硬化中的作用。方法：制备肾小球硬化动物模型,检测24小时尿蛋白定量、血浆白蛋白及血尿素氮水平,观察肾组织形态学改变;免疫组织化学检测TGF-β1、Smad2和Smad7蛋白水平;荧光定量PCR检测TGF-β1、Smad2和Smad7 mRNA的水平。结果：TGFβ1、Smad2和Smad7正常情况下普遍在肾小球系膜细胞、肾小管上皮及间质细胞中有少量表达;模型组4周时TGFβ1和Smad2蛋白表达增加,Smad7蛋白表达下降;6-8周时TGF-β1和Smad2蛋白表达明显增加,Smad7蛋白表达明显下降。模型组4周时TGF-β1和Smad2 mRNA出现表达上调,6~8周TGF-β1和Smad2mRNA表达明显增加。4周时Smad7 mRNA表达下调,6-8周Smad7 mRNA表达明显下降。模型组与对照组比较有显著性差异（p〈0.01）。结论：TGF-β/Smad信号通路参与了肾小球硬化的纤维化进程,Smad7是TGF-β/Smad信号通路抑制性调控因子,可能为治疗肾小球硬化提供治疗手段。

Objective：According to observe the expression of TGF-β,Smad2 and Smad7 in glomerulosclerosis model, investigate the significance of TGF-β/Smad Signaling Pathway in the development of glomerulosclerosis.Methods：36 rats were randomly divided into control group and model group.Adriamycin nephropathy was induced in rats in the model groups by intravenous injection of adriamycin.The levels of 24 h urine protein（Upr）,blood album（Alb）and blood urea nitrogen（BUN）of rats in each group were examined.The expression levels of TGF-β,Smad2 and Smad7 in renal tissue were detected by immunohistochemical method and fluorescent quantitation PCR.Results：TGF-β,Smad2 and Smad7 express fewly in mesangial cell,tubules epithelium and interstitial cell. The levels of TGFβ1,Smad2 protein and mRNA in renal tissue were increased in model group in the fourth,the sixth and the eighth week as compared with those in the control group.While the levels of Smad7 protein and mRNA were decreased gradually compared with control group.Conclusion：TGF-β/Smad Signaling Pathway Chinese participates in the development of glomerulosclerosis.Smad7 maybe the inhibitor of TGF-β/Smad Signaling Pathway,which will be a new therapy to glomerulosclerosis.