基础医学与临床 ›› 2016, Vol. 36 ›› Issue (7): 896-901.

• 研究论文 • 上一篇    下一篇

柚皮素通过抑制TGF-β1/smad信号传导通路缓解糖尿病肾病大鼠肾损伤

文利1,陈蕾1,孙一瑄1,段青蕊2,魏礼江1,周琴1,彭惠民1,张政1   

  1. 1. 重庆医科大学
    2. 第二临床学院
  • 收稿日期:2015-12-21 修回日期:2016-03-25 出版日期:2016-07-05 发布日期:2016-06-22
  • 通讯作者: 张政 E-mail:zhangzheng92@163.com
  • 基金资助:
    国家自然科学基金;重庆市科委一般项目

Naringenin ameliorates kidney injury by inhibitiing TGF-β1/smad signaling pathway in diabetic nephropathy rats

  • Received:2015-12-21 Revised:2016-03-25 Online:2016-07-05 Published:2016-06-22
  • Contact: 易红 E-mail:zhangzheng92@163.com

摘要: 目的 探讨柚皮素对糖尿病肾病大鼠肾脏的保护作用及其对TGF-β1/smad信号传导通路的影响。方法 将糖尿病肾病模型大鼠随机分为糖尿病肾病组和糖尿病肾病+柚皮素组,用药治疗6周。检测大鼠24 h尿蛋白定量、肌酐清除率和肾脏指数;HE染色观察肾组织形态和检测肾小球面积;实时荧光定量 PCR检测Ⅳ型胶原和纤维连接蛋白mRNA的表达;Western blot检测Ⅳ型胶原、纤维连接蛋白、TGF-β1、smad7、总smad2和磷酸化smad2蛋白。 结果 糖尿病肾病组大鼠24 h尿蛋白和肾脏指数显著升高,肌酐清除率明显下降(P<0.01),肾小球明显肥大(P <0.05),Ⅳ型胶原和纤维连接蛋白的mRNA水平和蛋白表达量均升高,TGF-β1和磷酸化smad2蛋白的表达量均升高,smad7蛋白表达量降低;经柚皮素50 mg/kg治疗后能明显降低糖尿病肾病大鼠的24 h尿蛋白(P <0.01)和肾脏指数(P <0.05),提高肌酐清除率(P <0.05),减轻肾小球肥大(P <0.05),Ⅳ型胶原和纤维连接蛋白的mRNA水平和蛋白表达量降低,TGF-β1和磷酸化smad2蛋白的表达量均降低,smad7蛋白表达量升高。结论 柚皮素可能通过调控糖尿病肾病肾组织TGF-β1/smad信号通路表达,减轻肾脏病理损害。

关键词: 柚皮素, 细胞外基质, TGF-β1/smad信号通路, 糖尿病肾病

Abstract: Objective To explore the protectory effects of naringenin (NAR) on kidney as well as its effects on TGF-β1/smad signaling pathway in diabetic nephropathy rats. Methods Experimental rats were randomly assigned into diabetic nephropathy group and naringenin group. After rats were treated with naringenin for 6 weeks, the 24 h-urinary protein (24 h-UP), Creatinine clearance rate (Ccr) and kidney index (KI) were detected. Glomerular pathological changes and glomerular area(GA) were observed by HE-straning. Type Ⅳ collagen(Col4)、fibronectin(FN) were detected by real-time PCR and Western blot. TGF-β1,smad7,t-smad2 and p-smad2 were detected by Western blot. Results Compared with CON group, the 24 h-UP (P <0.01), KI (P <0.01) and GA (P <0.05) were increased, whereas Ccr (P <0.01) was declined in DN group, the mRNA and protein of Col4 and FN were increased, the protein of TGF-β1 and p-smad2 were increased and smad7 was decreased. Naringenin treatment could significantly attenuated the renal lesion, inhibited the expression of Col4,FN,TGF-β1 and p-smad2, improved the expression of smad7. Conclusion Naringenin ameliorates renal function, has marked protectory effects on kidneys in diabetic nephropathy, possibly through inhibited the activation of TGF-β1/smad and reduced the deposition of ECM proteins.

Key words: naringenin, ECM, TGF-β1/Smad signaling, diabetic nephropathy

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