基础医学与临床 ›› 2014, Vol. 34 ›› Issue (2): 160-167.

• 研究论文 • 上一篇    下一篇

蛋白酶体抑制剂MG132减轻糖尿病大鼠肾小管间质纤维化

王圆圆1,刘丽荣1,李霜1,郭兵2,石磊1,石明隽2,肖瑛2   

  1. 1. 贵阳医学院
    2. 贵阳医学院病理生理学教研室
  • 收稿日期:2013-07-01 修回日期:2013-09-26 出版日期:2014-02-05 发布日期:2014-01-13
  • 通讯作者: 郭兵 E-mail:guobingbs@126.com
  • 基金资助:
    国家自然科学基金资助项目;贵州省社会发展科技攻关计划资助项目

Proteasome inhibitor MG132 improves the renal tubule-interstitium in diabetic rats

  • Received:2013-07-01 Revised:2013-09-26 Online:2014-02-05 Published:2014-01-13
  • Contact: Bing GUO, E-mail:guobingbs@126.com

摘要: 目的 探讨蛋白酶体抑制剂MG132是否减轻或延缓糖尿病肾病(DN)大鼠肾小管间质纤维化及其可能机制。方法 用链脲菌素复制糖尿病大鼠模型(DM),实验分为对照组(NC) 及DM组,每组n = 10。24周处死大鼠,检测相应生化指标,观察肾组织病理改变;体外培养NRK-52E细胞,予以不同剂量MG132预处理后高糖培养。免疫组化、免疫荧光染色、Western blot检测肾组织和NRK-52E细胞中Smad7、Smurf2、E钙黏蛋白(E-cadherin)和α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)及胶原蛋白(Col-Ⅰ)的表达。结果 与NC组相比,DM组大鼠肾组织E-cadherin减少(P<0.05)、α-SMA增多(P<0.05),FN及Col-Ⅰ蛋白在间质沉积增多(P<0.05),而Smad7蛋白减少(P<0.05), Smurf2表达增加(P<0.05)。MG132 抑制了高糖诱导的NRK-52E细胞α-SMA和Col-Ⅰ蛋白的表达(P<0.05),并呈量效依赖性,但对Smurf2的蛋白表达无影响;相反,MG132上调了Smad7蛋白及E-cadherin的表达(P<0.05)。结论MG132减缓糖尿病大鼠肾小管间质纤维化。

关键词: 糖尿病肾病, 肾纤维化, Smad7, MG132

Abstract: Objective To investigate proteasome inhibitor MG132 whether or not to reduce or slow down the renal tubule-interstitium during diabetic nephropathy (DN). Methods The diabetic rat model(DM) was established by injecting Streptozotocin(STZ) (n = 10). Meanwhile, ten rats were grouped into normal control group (NC). After 24 weeks, the rats were sacrificed to detect relevant biochemical parameters, and to observe the changes of pathomorphology of kidney and pancreas as well. NRK-52E cells were cultured in vitro, to be pre-treated with different doses MG132 cultured in high glucose. In addition, immunohistochemistry and immunofluorescence staining, Western blotting were employed to detect the protein expression of Smad7, Smad ubiquitin regulatory factor 2(Smurf2), E-cadherin (E-cadherin) and α-smooth muscle actin (α-SMA) and fibronectin (FN), collagen-Ⅰ (Col-1)in the renal tissue and NRK-52E cells. Results Compared with NC group,the expression of E-cadherin decreased and α-SMA increased in DM group (P <0.05). In DM group, the expressions of FN and Col-1 in renal interstitium were increased (P < 0.05), while the protein expression of Smad7decreased (P <0.05),but Smurf2 was increased (P <0.05). In vitro, MG132 inhibited the protein expressions of α-SMA and Col-Ⅰby a dose-dependent manner which were induced by high glucose in NRK-52E cells (P <0.05), but it had no effect with the protein expression of Smurf2.In contrary, MG132 increased the protein expression of Smad7 and E-cadherin (P <0.05). Conclusion MG132 inhibited the protein degradation of Smad7 which high glucose-mediated, could reduce the development of the renal tubule-interstitium, this may be one of the mechanisms that MG132 could treat DN.

Key words: Diabetic nephropathy, Renal fibrosis, Smad7, MG132

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