MG132可增强糖尿病大鼠肾脏抗氧化能力  

MG132 enhances the renal anti-oxidative ability in diabetic nephropathy rats

作　　者：罗志锋[1] 齐伟[1] 曾薇[1] 庞琦[1] 郭艳红[1] 牟娇[1] 冯兵[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037

出　　处：《中华肾脏病杂志》2011年第3期209-214,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30570763,30900690）

摘　　要：目的探讨蛋白酶体抑制剂MG132对糖尿病肾病（DN）大鼠的治疗作用及其机制。方法72只大鼠随机分为正常对照组（NC）、DN组和MG132治疗组（DN＋MG132），每组各24只。在治疗第4、8和12周末检测各组大鼠24h尿蛋白排泄率（UPER）、24h尿量和尿丙二醛（MDA）含量、肾组织26S蛋白酶体、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—PX）活性；实时荧光定量PCR法检测各组大鼠肾组织SOD、GSH—PX和p47phoxmRNA的表达变化；Western印迹检测p47phox的蛋白表达变化。结果与Nc组大鼠比较，在4、8和12周时，DN大鼠的UPER显著增高（均P〈0．05）；12周时病理显示DN组大鼠肾小球系膜显著增生和系膜基质积聚增多。与同期DN组大鼠比较，MG132治疗组大鼠的UPER显著降低（均P〈0．05），肾小球系膜增生和基质积聚均减少。在4、8和12周，DN组大鼠肾组织26S蛋白酶体活性比NC组分别增高了2．14倍、2．66倍和3．68倍（均P〈0．05）。与DN组大鼠比较，MG132治疗组大鼠26S蛋白酶体活性显著下降（均P〈0．05）。与NC组大鼠相比，DN组大鼠肾组织p47phoxmRNA表达分别升高了1：55％、149％和120％（均P〈O．05）；p47phox蛋白表达分别升高了139％、152％和186％（均P〈0．05）；尿MDA含量分别升高了1．95倍、2．04倍和2．62倍（均P〈0．05）；而DN大鼠肾组织SOD活性分别下降23．09％、33．59％和53．31％（均P〈0．05）；GSH—PX的活性分别下降28．57％、33．06％和48．76％（均P〈0．05）；SODmRNA表达分别下降38．09％、61．44％和76．53％（均P〈0．05），GSH．PXmRNA表达分别下降29．16％、37．26％和62．40％（均P〈0．05）。与1）N组大鼠比较，MG132治疗组大鼠肾组织D47phoxmRNA和蛋白表达以及尿MDA含量则显著下降（均P〈0．05），而SOD和GSH—PX的活性和mRNA均显著升高（均P〈0．05）。结论MG132对DN大鼠肾脏有显著的保�Objective To investigate the effects of MG132 on diabetic nephropathy （DN） rats induced with streptozocin. Methods Seventy-two male SD rats were randomly divided into three groups： normal control group （NC, n=24）, I）N group （n=24） and DN treated with MG132 group （DN＋MG132, n=24）. At the end of 4, 8 and 12 weeks, 24 hour urinary protein excretion rate （UPER） was detected. Morphology of kidney was examined by special staining of periodic acidschiff （PAS）. Renal 26S proteasome activity was determined by quantifying the hydrolysis of SLLVY-AMC in a fluorescence reader. Urinary malondialdehyde （MDA） level and renal SOD and GSH-PX activity were detected by commercial kits. Renal SOD, GSH-PX and p47phox mRNA expressions were determined by real-time fluorescence PCR. Renal p47phox protein expression was determined by Western blotting. Results Compared with NC group, the DN group showed a significant increased of UPER at week 4, 8, 12 （all P〈0.05）, of mesangium proliferation and mesangial matrix expansion at week 12. In DN＋MG132 group, UPER was significantly decreased compared with DN group at the end of 4, 8 and 12 weeks （P〈0.05, respectively）, and the glomernler pathological alteration induced by diabetes was attenuated. Increased renal 26S proteasome activity in DN rats was significantly inhibited after MG132 administration （P〈0.05）. Moreover, renal p47phox mRNA expression in DN group was 155%, 149% and 120% more than those in NC group at 3 time points （all P〈0.05）, and so was the renal p47phox protein expression, 139%, 152% and 186% more （all P〈0.05）. Urinary MDA levels in DN group were 1.95-, 2.04- and 2.62-folds more than those in NC group （all P〈0.05）. In addition, compared with NC group at 3 time points, in DN group, renal SOD activity was decreased by 23.09%, 33.59% and 53.31% （all P〈0.05）; renal GSH-PX activity was decreased by 28.57%, 33.06% and 48.76% （all P〈 0.05）; renal SOD mRNA was decreased by 38.09%, 61.44% and 76.53% （a

关 键 词：糖尿病肾病 氧化性应激 抗氧化剂 蛋白酶体 MG132 

分 类 号：R285.5[医药卫生—中药学]