蛋白酶体抑制剂MG132抑制糖尿病肾脏疾病机制的研究  

Study on mechanisms involved in protease inhibitor MG132 inhibiting diabetic kidney disease

作　　者：王圆圆[1] 张小欢[1] 毛彦稳 刘玲伶[1] 彭伟 刘慧铭 石明隽[1] 肖瑛[1] 张莹莹[1] 郭兵[1] 

机构地区：[1]贵州医科大学病理生理学教研室贵州医科大学重大疾病发病机制及药物防治特色重点实验室,贵阳550025

出　　处：《中国糖尿病杂志》2018年第2期139-143,共5页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81541102);贵州省科技厅联合基金(黔科合LH字[2015]7335);贵阳市科技局基金(筑科合同[20151001]社14号);贵阳医学院博士启动基金(院博合J字[2014]008)

摘　　要：目的探讨蛋白酶体抑制剂MG132是否抑制糖尿病肾脏疾病(DKD)的发展及其可能的机制。方法 STZ复制糖尿病大鼠,随机分为糖尿病组(DM组,n=9)、MG132治疗组(MG132组,n=9),MG132组从第9周起予MG 132[0.1mg/(kg·d)]腹腔注射治疗糖尿病大鼠。同时设对照(Con组,n=9)组,检测生化指标,观察肾组织病理改变;Western blot检测肾组织SnoN、第10号染色体缺失的磷酸酶和张力蛋白同源基因(PTEN)、钙黏蛋白(E-cadherin)和α-平滑肌肌动蛋白(α-SMA)的表达。结果与Con组比较,DM组血糖[(5.85±0.86)vs(17.49±1.21)mmol/L,P=0.00]、尿微量白蛋白/尿肌酐比值(UACR)[(1.11±0.29)vs(16.36±3.06)mg/mmol,P=0.00]、肾脏指数(KW/BW)[(6.32±0.49)vs(14.54±1.49)mg/g,P=0.00]明显增加,且肾小管间质纤维化病变明显,α-SMA[(0.18±0.03)vs(0.33±0.02),P=0.002)增多,而SnoN[(0.87±0.10)vs(0.32±0.11),P=0.007)、PTEN[(2.06±0.09)vs(1.26±0.06),P=0.00]、E-cadherin[(1.32±0.06)vs(0.50±0.03),P=0.00]减少;MG132治疗后,UACR[(6.74±3.47)mg/mmol,P=0.003]、KW/BW[(12.43±1.11)mg/g,P=0.01]降低,纤维化病变减轻,α-SMA[(0.19±0.05),P=0.003]减少,SnoN[(0.55±0.09),P=0.033]、PTEN[(1.73±0.15),P=0.002]、E-cadherin[(1.11±0.10),P=0.00]蛋白的表达增加。结论 MG132可能通过恢复SnoN、PTEN蛋白水平抑制DKD的发展。Objective To explore whether treatment with protease inhibitor MG132 would reduce the fibrosis of the renal tubule of Diabetic kidney disease （DKD）and what the possible mechanisms involved in. Methods The diabetic rat model was established by tail-vein injecting Streptozotocin （STZ） in 18 male SD rats and then were divided into 2 groups：9 without treatment （DM group）, 9 treated with MG132 [0. 1 mg/（kg · d）]by intraperitoneal injection （MG132 group）. Another 9 SD rats were set as normal control group （Con group）. After 16 weeks, the rats were sacrificed to detect relevant biochemical parameters, and to observe the changes of pathomorphology of kidney. In addition, western blotting was employed to detect the protein expression of SnoN.（Ski-related novel protein N）, PTEN （Phosphatase and tensin homology deleted on chromosome ten）, E-cadherin and a-SMA （a-smooth muscle actin）, respectively. Results Compared with Con group, the levels of blood glucose [ （5.85 ± 0.86） vs （17.49tl. 21）mmol/L,P=0.00] ,urinary albumin/creatinine （UACR）[,（1.11±0.29） vs （16.36±3.06） mg/mmol, P= 0. 00], kidney index （KW/BW） [, （ 6.32 ± 0.49 vs （ 14.54 ± 1.49 ） mg/g, P = 0.00） were increased remarkably in DM group. Pathological detection on kidneys indicated that renal tubule fibrosis was obvious. The expression of a-SMA [-（0.18 ± 0.03） vs （0.33 ± 0. 02）, P = 0. 002] in kidney was increased in DM group, and the expression of SnoN [ （0.87 ±0.10） vs （0.32±0.11）, P = 0. 007], PTEN [-（2. 06±0.09） vs （1.26±0. 06） ,P=0.00] and E-cadherin [,（1.32±0.06） vs （0. 50t0.03） ,P=0.00] were significantly reduced. Compared with DM group, the levels of UACR [-（6.74±3.47） mg/mmol, P = 0. 003] and kidney index [,（12.43±1. 11）mg/g,P=0.01] were reduced significantly in MG132 group,and the alleviated renal fibrosis was observed by light microscope. The protein expression of a-SMA E（0.19± 0.05） ,P=0. 003] in MG132group was decreased compa

关 键 词：糖尿病肾脏疾病 肾脏纤维化 蛋白酶体抑制剂MG132 SNON 第10号染色体缺失的磷酸酶和张力蛋白同源基因 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]