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大豆异黄酮对 2 型糖尿病大鼠肾组织中 Wnt/β-catenin 及 TGF-β1 信号通路的影响。

Effects of soybean isoflavones on Wnt/β-catenin and the TGF-β1 signaling pathway in renal tissue of type 2 diabetic rats.

机构信息

Department of Histology and Embryology, Mudanjiang Medical University, Mudanjiang, Heilongjiang, People’s Republic of China.

Department of Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang, People’s Republic of China.

出版信息

J Biol Regul Homeost Agents. 2018 May-Jun;32(3):455-464.

Abstract

To observe the effect of Soyisoflavones (SI) on the expression of Wnt/β-catenin signaling pathway elements, transforming growth factor-β (THGF-β) and its related proteins in the renal interstitia of diabetic nephropathic (DN) rats, 48 DN rats were randomly divided into 4 groups: DN model group (group DN), soybean isoflavone treatment group (group DA), DN model group + losartan treatment group (group DL), DN model group + soybean isoflavones combined with losartan treatment group (group SL). Each group comprised 12 rats. Twelve healthy Wistar rats were selected as normal controls (group N). After 12 weeks of continuous administration of soybean isoflavone or losartan or those two combined, the body weight of rats was recorded and serum urea nitrogen (BUN) and creatinine (Scr) were measured. The expression of Wnt4, β-catenin, and TGF-β1 proteins, as well as mRNA, in the renal interstitium were detected by immunohistochemistry and real-time quantitative PCR (FQ-PCR). In all the groups, Wnt4, β-catenin and TGF-β1 protein were only expressed in renal interstitial and renal tubular epithelial cells. There was no significant difference between group DA and group DL (P>0.05). FQ-PCR results showed that Wnt4, β-catenin and TGF-β1 mRNA were consistent with the expression of these proteins in the renal tissue of each group. Soy isoflavones can reduce 24-h urinary protein quantification, alleviate renal interstitial pathological damage, and regulate the expression of Wnt4, β-catenin and TGF-β1 in the renal interstitium. This suggests that soybean isoflavones could delay the process of renal interstitial fibrosis in DN rats by decreasing the expression of Wnt4, β-catenin and TGF-β1 in the renal interstitium, thus demonstrating that soybean isoflavones plus losartan have the best protective effects against diabetes-induced renal fibrosis.

摘要

为了观察大豆异黄酮(SI)对糖尿病肾病(DN)大鼠肾间质 Wnt/β-连环蛋白信号通路相关因子、转化生长因子-β(THGF-β)及其相关蛋白表达的影响,将 48 只 DN 大鼠随机分为 4 组:DN 模型组(DN 组)、大豆异黄酮治疗组(DA 组)、DN 模型组+氯沙坦治疗组(DL 组)、DN 模型组+大豆异黄酮联合氯沙坦治疗组(SL 组),每组 12 只。另选 12 只健康 Wistar 大鼠作为正常对照组(N 组)。连续给予大豆异黄酮或氯沙坦或两者联合干预 12 周后,记录大鼠体质量,检测血清尿素氮(BUN)、肌酐(Scr),采用免疫组化法和实时荧光定量 PCR(FQ-PCR)法检测肾间质 Wnt4、β-连环蛋白、TGF-β1 蛋白及其 mRNA 的表达。结果显示,各组 Wnt4、β-连环蛋白和 TGF-β1 蛋白仅在肾间质和肾小管上皮细胞中表达,DA 组与 DL 组比较差异均无统计学意义(P>0.05)。FQ-PCR 结果显示,Wnt4、β-连环蛋白和 TGF-β1 mRNA 与各组肾组织中蛋白表达一致。大豆异黄酮可减少 24 h 尿蛋白定量,减轻肾间质病理损伤,调节肾间质 Wnt4、β-连环蛋白和 TGF-β1 的表达。表明大豆异黄酮可能通过降低肾间质 Wnt4、β-连环蛋白和 TGF-β1 的表达,延缓 DN 大鼠肾间质纤维化进程,且大豆异黄酮联合氯沙坦的保护作用最佳。

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