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两种植物雌激素对5/6肾切除鼠残余肾组织α-平滑肌肌动蛋白沉积的影响及机制探讨

Effects of phytoestrogens on the deposition of α-SMA in 5/6 nephrectomized rats and its related mechanism

摘要目的 探讨金雀异黄素、大豆黄素2种主要的植物雌激素对5/6肾切除鼠残余肾组织α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)沉积的影响及其机制.方法 32只鼠作5/6肾切除,将术后2周存活的27只鼠分为金雀异黄素组(9只)、大豆黄素组(10只)和对照组(8只),另有8只为假手术组.检测各组术前、术后第4、8周生化指标.观察第8 周肾组织的病理改变情况,应用免疫组化法检测肾组织中α-SMA的沉积情况,采用RT-PCR法和Western Blot法检测肾组织中转化生长因子-β1(TGF-β1)mRNA转录以及蛋白质表达情况.结果 与对照组相比,金雀异黄素组和大豆黄素组尿蛋白排泄量明显减少,血肌酐、尿素氮水平下降(P<0.01),肾小球硬化程度明显减轻,肾小球内α-SMA沉积显著减少,TGF-β1 mRNA及其蛋白质表达明显减弱(P<0.05).结论 金雀异黄素和大豆黄素可以降低5/6肾切除鼠残肾组织α-SMA的沉积,原因可能与抑制TGF-β1的表达有关.

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abstractsObjective To study the effect of genistein and daidzein, the 2 main phytoestrogens, on the deposition of α-smooth muscle actin (α-SMA) in 5/6 nephrectomized rats and its related mechanism. Methods The 5/6 nephrectomized rats were randomly divided into the genistein group (n=9), the daidzein group (n=10), the control group (n=8), and still another 8 rats with sham-operation were used as control. Urinary protein, serum albumin, total protein, creatinine, urea were measured both before operation and 4 and 8 weeks after operation. Pathologic changes in the kidney were investigated. Immunohistochemistry was employed to investigate the expression of α-SMA. RT-PCR and Western Blot were also used to measure mRNA transcription and protein expression of transforming growth factor-β1 ( TGF-β1 ) respectively. Results Urinary albumin excretion, serum creatinine and urea in the genistein and daidzein groups decreased substantially when compared with those of the control group (P<0.01). Pathological lesion of the genistein group was less serious than that of the control group. The deposition of α-SMA was lower than that of the control group. Protein expression and mRNA transcription of TGF-β1 in the operated groups were attenuated by genistein and daidzein (P<0.05). Conclusions Genistein and daidzein could decrease the deposition of α-SMA, and this might be associated with the inhibition of the expression of TGF-β1.

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