蛋白酶体抑制剂MG132减轻糖尿病大鼠肾小管间质纤维化  

Proteasome inhibitor MG132improves the renal tubule-interstitium in diabetic rats

作　　者：王圆圆[1] 刘丽荣[1] 李霜[1] 郭兵[1] 石磊[1] 石明隽[1] 肖瑛[1] 

机构地区：[1]贵阳医学院病理生理学教研室,贵州贵阳550004

出　　处：《基础医学与临床》2014年第2期160-167,共8页Basic and Clinical Medicine

基　　金：国家自然科学基金(81160094);贵州省社会发展科技攻关计划(黔科合SY字【2012】3088);贵阳医学院研究生教育创新计划(B201103)

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。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 ）. After 24 weeks, the rats were sacrificed 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 stai- ning, Western blot were employed to detect the protein expression of Smad7, Smad ubiquitin regulatory factor 2 （ Smurf2 ）, E-cadherin （E-cadherin） and or-smooth muscle actin （et-SMA） and fibronectin （ FN）, collagen- I （Col- I ）in the renal tissue and NRK-52E cells. Results Compared with NC group,the expression of E-cadherin decreased and ot-SMA increased in DM renal interstitium were increased （ P 〈 0. group （P 〈 0.05 ）. In DM group, the expressions of FN and Col- I in 05 ）, while the protein expression of Smad7 decreased （ P 〈 0. 05 ）, butSmurf2 was increased （P 〈0.05）. In vitro, MG132 inhibited the protein expressions of α-SMA and Col- I by 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-eadher- in （P 〈 0. 05 ）. Conclusions MG132 inhibites protein degradation of Smad7 induced by high glucose and reduces renal tubule-interstitium.

关 键 词：糖尿病肾病 肾纤维化 SMAD7 MG132 

分 类 号：R587.1[医药卫生—内分泌]