基础医学与临床 ›› 2018, Vol. 38 ›› Issue (2): 194-199.

• 研究论文 • 上一篇    下一篇

WNT4及其抑制因子SFRP1在糖尿病肾病大鼠肾组织中的表达

孔静1,田平平1,李圆圆2,石明隽1,王圆圆1,肖瑛1,张帆1,郭兵1,孙兰1   

  1. 1. 贵州医科大学病理生理学教研室
    2. 江苏医药职业学院病理学与病理生理学教研室
  • 收稿日期:2017-08-08 修回日期:2017-11-08 出版日期:2018-02-05 发布日期:2018-01-24
  • 通讯作者: 石明隽 E-mail:1967171727@qq.com
  • 基金资助:
    贵州省教育厅(招标项目); 贵州省卫生计生委; 贵州省科技厅攻关项目

Expression of WNT4 and its inhibitory factor SFRP1 in renal tissue of diabetic nephropathy rats

  • Received:2017-08-08 Revised:2017-11-08 Online:2018-02-05 Published:2018-01-24

摘要: 目的 观察WNT4/β-catenin信号通路及其抑制因子分泌型卷曲相关蛋白1(SFRP1)在糖尿病肾病(DN)大鼠肾组织中的表达变化,探讨其在肾脏纤维化发生发展中的可能作用。方法 将大鼠随机分为正常对照(NC)组和DN组,8只/组。尾静脉注射STZ 55 mg/kg复制IDDM模型。HE、PAS及Masson染色观察肾组织形态学结构和纤维化病变;免疫组织化学法观察WNT4和β-catenin蛋白在肾组织的表达部位;Western blot检测WNT4、SFRP1、β-catenin、p-GSK-3β、GSK-3β、CollagenⅠ、α-SMA和E-cadherin蛋白在肾组织中的表达;Real-time PCR检测WNT4及SFRP1 mRNA在肾组织中的表达。结果 与NC组相比,DN组大鼠肾组织纤维化病变明显;WNT4蛋白和mRNA表达显著增多(p<0.05);β-catenin、p-GSK-3β、α-SMA和CollagenⅠ蛋白的表达显著增多(p<0.05);E-cadherin蛋白表达显著减少(p<0.05);SFRP1蛋白和mRNA表达显著下降(p<0.05)。结论 在DN发病中,WNT4/β-catenin信号通路异常活化;SFRP1表达减少可能抑制该通路,促进了DN肾纤维化的发生发展。

关键词: SD大鼠, 糖尿病肾病, WNT4, β-连环蛋白, 分泌型卷曲相关蛋白

Abstract: Objective To observe the change of expression of WNT4/β-catenin signaling pathway and its inhibitory factor Secreted frizzled-related protein 1 (SFRP1) in renal tissue in diabetic nephropathy(DN) rats, and to explore its possible role in the development of renal fibrosis. Methods Rats were randomly divided into normal control (NC) group and DN group, and was equipped with 8 in each group. The IDDM model was prepared by tail vein injection of STZ 55 mg/kg. Hemotoxyin and eosin、Periodic Acid-Schiff and Masson stain was used to observe the morphological structure and fibrotic lesions in renal tissue; Immunohistochemical analysis was used to observe the protein expression of WNT4 and β-catenin in renal tissue; Western blot was used to detect the protein expression changes of WNT4, SFRP1, β-catenin , p-GSK-3β, GSK-3β, CollagenⅠ, α-SMA, E-cadherin in renal tissue in each group; The mRNA expressions of WNT4 and SFRP1 in renal tissues of rats were detected by real-time PCR. Results Compared with NC group, renal tissue fibrosis was obvious in DN group. Compared with NC group,The protein and mRNA expressions of WNT4 significantly increased (p<0.05), and the protein expressions of β-catenin, p-GSK-3β, α-SMA and CollagenⅠsignificantly increased (p<0.05), and the protein expressions of E-cadherin significantly decreased (p<0.05), and the protein and mRNA expressions of SFRP1 significantly decreased (p<0.05). Conclusions In the case of DN, the signal pathway of WNT4/β-catenin was abnormal activation. The expression of SFRP1 is decreased that may inhibit this pathway and promote the development of renal fibrosis in DN.

Key words: SD rat, Diabetic nephropathy, WNT4, β-catenin, SFRP1

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