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目的探讨转化生长因子β1(TGF—β1)及其信号转导分子Smad2、Smad3、细胞外基质(ECM)在肾小球硬化过程中的表达及其意义。方法以20例正常肾组织为对照组,对38例各种不同组织学类型的肾活检标本,用免疫组织化学染色方法观察TGF—β1、Smad2、Smad3、纤连蛋白(FN)在肾小球中的染色强度,并对检测结果作图像分析处理。以体外培养的人系膜细胞为对象,观察TGF-β1对系膜细胞表达Smad2、Smad3、FN的影响。Smad2、Smad3、FN的基因表达采用RT—PCR检测;Smad2、Smad3、FN的蛋白表达采用Western印迹检测。结果所有增生、硬化病理类型肾小球肾炎中病变肾小球TGF—β1、Smad2、Smad3、FN蛋白表达均显著高于对照组(P<0.05),且TGF—β1、Smad2、Smad3在肾小球中的表达与FN在肾小球中的蓄积呈显著正相关(P<0.05)。外源性TGF—β1刺激人肾系膜细胞后,系膜细胞Smad3mRNA和蛋白表达显著增高(P<0.05);Smad2mRNA和蛋白表达无明显改变(P>0.05);FNmRNA和蛋白表达显著增高(P<0.05)。结论TGF—β1及其信号转导分子Smad蛋白可能参与了ECM在病变肾小球中的过量蓄积,从而在肾小球硬化过程中起重要作用。
Objective To investigate the expression and significance of transforming growth factor β1 (TGF-β1) and its signal transduction molecules Smad2, Smad3 and extracellular matrix (ECM) during glomerulosclerosis. Methods Twenty normal renal tissues were used as control group. Thirty-eight renal biopsy specimens of various histological types were observed by immunohistochemical staining for the expression of TGF-β1, Smad2, Smad3 and fibronectin (FN) In the staining intensity, and test results for image analysis. To investigate the effect of TGF-β1 on the expression of Smad2, Smad3 and FN in human mesangial cells cultured in vitro. The gene expression of Smad2, Smad3 and FN was detected by RT-PCR. The protein expression of Smad2, Smad3 and FN was detected by Western blotting. Results The expressions of TGF-β1, Smad2, Smad3 and FN in glomeruli of glomerulonephritis were significantly higher than those in control group (P <0.05), and the expressions of TGF-β1, Smad2 and Smad3 in glomeruli There was a significant positive correlation between the expression of FN and glomerular accumulation (P <0.05). The expression of Smad3 mRNA and protein in mesangial cells was significantly increased (P <0.05), and the expression of Smad2 mRNA and protein was not significantly changed (P> 0.05), and the expression of FN mRNA and protein was significantly increased in human mesangial cells stimulated by exogenous TGF-β1 (P <0.05). Conclusion TGF-β1 and its signal transduction molecule Smad may be involved in the excessive accumulation of ECM in glomerular lesions, which play an important role in glomerulosclerosis.