叔丁基对苯二酚对糖尿病小鼠肾脏氧化应激损伤及Nrf2蛋白表达的影响  

Effects of tBHQ on the oxidative stress and the expression of Nrf2 in kidneys of diabetic mice

作　　者：李航[1] 任韫卓[1] 刘淑霞[1] 刘青娟[1] 刘品力[2] 周琰[3] 段惠军[1] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017 [2]河北医科大学附属第二医院检验科,河北石家庄050000 [3]河北省石家庄市中心医院检验科,河北石家庄050011

出　　处：《中国药理学通报》2009年第10期1341-1345,共5页Chinese Pharmacological Bulletin

基　　金：河北省自然科学基金资助项目(NoC2006000825)

摘　　要：目的研究叔丁基对苯二酚(tBHQ)对早期糖尿病小鼠肾脏Nrf2-ARE信号通路表达及氧化应激的影响,探讨tBHQ保护肾脏的部分机制。方法CD-1♂小鼠随机分为3组,对照组(C组)、糖尿病组(DM组)、tBHQ干预组(DM+tBHQ组)。腹腔注射STZ诱发糖尿病小鼠模型,DM+tBHQ组在成模3d后给予添加了1%tBHQ(W/W)的饲料喂养,4wk后检测3组动物的血糖、肾功能、24h尿白蛋白定量、血清及肾皮质丙二醛(MDA)含量。免疫组化和Westernblot检测Nrf2,HO-1蛋白在肾组织的定位和表达水平。结果①DM组小鼠血尿素氮、24h尿白蛋白定量、肾重/体重,血清及肾皮质MDA含量较C组升高。tBHQ干预组上述指标均降低。②与DM组相比,tBHQ干预组肾皮质总蛋白Nrf2、HO-1及核蛋白Nrf2表达水平明显增高;免疫组织化学检测显示Nrf2于肾小管及肾小球的胞质及胞核内均有表达;HO-1主要表达于肾小管上皮细胞胞质中。结论tBHQ减轻了早期糖尿病小鼠肾脏的氧化应激损伤,其作用机制可能是部分通过激活Nrf2-ARE信号通路进而增强抗氧化蛋白HO-1的表达而实现的。Aim To observe the protective effects of tBHQ（ transcription factor Nrf2 promoter）on oxidative stress in early diabetic mice and to study the possible mechanisms underlying tBHQ＇ s protection against diabetic nephropathy. Methods Male CD-1 mice were randomly divided into three groups：control group（ group C） diabetic group （ group DM） ; tBHQ treated group （ group DM ＋ tBHQ）. The mice of group DM and group DM ＋ tBHQ were induced by single-dose intraperitoneal injection of streptozocin（STZ） and after 3 days mice of group DM ＋ tBHQ were treated with 1% tBHQ food （W/W） for 4 weeks. Mice of the three group were assessed for changes in blood glucose, kidney function,24 hour urine albumins,levels of MDA of the serum and renal cortex. The protein location and expression of Nrf2, HO-1 in kidney was observed by immunohistochemistry and Western blot. Results （1） Compared with group C, the levels of blood urea nitrogen, 24 hours urine albumins, KW /BW and serum, cortical MDA content were increased in the DM models. All these parameters were remarkably improved with tBHQ intervention ;（2） Compared with group DM,total protein of Nrf2, HO-1 and nucleus protein of Nrf2 were significantly increased in group DM ＋ tBHQ by Western blot. Immunohistochemistry staining studies indicated that Nrf2 was presented in both nuclear and cytoplasm of renal glomerulus and tubular cells; HO-1 protein was mainly expressed in cytoplasm of renal tubular cells. Conclusions tBHQ attenuates the oxidative stress in mice diabetic nephropathy. The beneficial effect may be mediated by activating transcription factor Nrf2 and at least in part, elevating the expression of antioxidative protein HO-1.

关 键 词：糖尿病 糖尿病肾病 氧化应激 NRF2 HO-1 叔丁基对苯二酚 

分 类 号：R-332[医药卫生] R322.61