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目的:探讨转化生长因子β(TGF-β1)及其信号转导分子Smad4在肾小球肾炎中的表达及其意义。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肾小球肾炎的肾活检标本,分别行免疫组化方法观察TGF-β1、Smad4、胶原Ⅰ(collagentypeⅠ)在肾小球中的染色强度,并对其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TGFβ1对系膜细胞表达Smad4、胶原Ⅰ的影响,Smad4、胶原Ⅰ的基因表达用RT-PCR检测,蛋白表达用Westernblotting检测。结果:所有增生、硬化病理类型肾炎中病变肾小球TGFβ1、Smad4、胶原Ⅰ蛋白表达均高于对照组(P<0.05),且TGFβ1、Smad4两者在肾小球中的表达与胶原Ⅰ在肾小球中的堆积呈多重相关(P<0.05);外源性TGFβ1刺激人肾系膜细胞后,细胞的Smad4基因表达和蛋白表达增高(P<0.05);胶原Ⅰ的基因表达和蛋白表达也相应增高(P<0.05)。结论:TGFβ1及其信号转导分子Smad4可能参与病变肾小球ECM的过量堆积,在肾小球硬化过程中起重要作用。
Objective: To investigate the expression of transforming growth factor β (TGF-β1) and its signal transduction molecule Smad4 in glomerulonephritis and its significance. Methods: Twenty normal renal tissues were used as control group. Immunohistochemistry was used to examine the expression of TGF-β1, Smad4 and collagenype Ⅰ in 38 renal biopsy specimens of various histological types of glomerulonephritis. The intensity of staining in pellets was analyzed by image analysis. The cultured human mesangial cells were treated with TGFβ1. The effect of TGFβ1 on the expression of Smad4 and collagen Ⅰ was observed. The expression of Smad4 and collagen Ⅰ RT-PCR detection, protein expression detected by Westernblotting. Results: The expressions of TGFβ1, Smad4 and collagen Ⅰ in glomeruli were higher than those in control group (P <0.05), and the expressions of TGFβ1 and Smad4 in glomeruli were higher than those in collagen Ⅰ (P <0.05). The expression of Smad4 gene and protein were increased in human renal mesangial cells stimulated by exogenous TGFβ1 (P <0.05). The gene expression and protein expression of collagen Ⅰ Also increased accordingly (P <0.05). Conclusion: TGFβ1 and its signal transduction molecule Smad4 may be involved in excessive accumulation of glomerular lesions in glomeruli and play an important role in glomerulosclerosis.