普罗布考对糖尿病肾病大鼠氧化应激的影响  

Effects of probucol on oxidative stress in rats with diabetic nephropathy

作　　者：战云飞[1] 陈淑红[2] 郑少雄[3] 

机构地区：[1]山东省胸科医院内科,济南250013 [2]山东省临沂市人民医院内分泌科,276000 [3]天津医科大学第二医院内分泌代谢科,300211

出　　处：《国际内分泌代谢杂志》2012年第6期365-368,F0003,共5页International Journal of Endocrinology and Metabolism

摘　　要：目的观察普罗布考（PB）对糖尿病肾病（DN）大鼠氧化应激的影响。方法60只Sprague—Dawley（SD）雄性大鼠随机分成4组：正常对照组（NC组）8只，右肾血管结扎组（RL组）8只，DN组22只，DN＋PB组22只。RL组、DN组和DN＋PB组首先进行右肾血管结扎，1周后DN组和DN＋PB组应用50mg／kg四氧嘧啶行尾静脉注射，72h测血糖高于16．7mmol／L视为糖尿病造模成功入组，造模成功率为82．5％。DN＋PB组给予每天1次170mg／kgPB灌胃，共3周。实验结束时NC组8只，RL组6只，DN组5只，DN＋PB组8只。收集24h尿量，处死各组大鼠并检测24h尿微量白蛋白（24hUMA）、肾脏肥大指数（LK／BW）、血糖、血尿素氮（BUN）、肌酐（Cr）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）、高密度脂蛋白（HDL）水平，同时测定丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH—PX）的活性。左侧肾脏行HE染色病理检查。结果与NC组和RL组相比，DN组、DN＋PB组的血糖、LK／BW明显升高（P〈0．05）；与NC组、RL组、DN＋PB组相比，DN组的BUN、Cr、24hUMA、LDL、MDA明显升高（P〈0．05），SOD、CAT、SOD／MDA明显降低（P〈0．05）。与DN组相比，DN＋PB组上述指标则明显改善。与NC组相比，RL组、DN组、DN＋PB组的GsH—PX均升高（P〈0．05），而RL组、DN组和DN＋PB组3组之间无统计学差异（P〉0．05）。4组之间TC、TG、HDL、VLDL无差别（P〉0．05）。相关分析表明BG、BUN、Cr、24hUMA、LK／BW、LDL与MDA呈正相关（均P〈0．01），与SOD、SOD／MDA均呈负相关（均P〈0．01）。肾组织病理提示DN＋PB组较DN组在。肾小球增大、基底膜增厚、肾小球系膜基质增生、动脉壁增厚方面有所改善。结论MDA和SOD／MDA是衡量氧化和抗氧化的敏感指标，PB可以提高DN大鼠体内抗氧化酶的活�Objective To investigate the antioxidant effects of probucol（PB） on oxidative stress in diabetic nephropathy（DN） rats. Methods 60 Sprague-Dawley （SD） male rats were randomly divided into four groups： normal control group（ NC group, n = 8 ）, right renal blood vessel ligation group （RL group, n = 8 ）, DN group（ n = 22 ）, DN ＋ PB group （n = 22）. The right renal blood vessels were ligated in RL group, DN group and DN ＋ PB group. After a week the diabetic model was established by intravenous injection of alloxan with the dose of 50 mg/kg in DN group and DN ＋ PB group. 82.5% of rats whose 72 h blood glucose level were higher than 16.7 mmol/L were considered to be valid diabetic models. The rats in DN ＋ PB group were administrated with PB 170 mg/（kg · d） by a gastric tube for 3 weeks. The rats survived to the end of the ex- periment were 8 in NC group,6 in RL group,5 in DN group,8 in DN ＋ PB group. 24 h urine was collected be- fore the rats were sacrificed. 24 h urinary microalbumin （ UMA）, the kidney hypertrophy index （ LK/BW）, blood glucose （ BG）, blood urea nitrogen （ BUN ）, creatinine （Cr）, total cholesterol （ TC ）, triglyceride （ TG）, low density lipoprotein （ LDL ）, very low density lipoprotein （ VLDL ）, high density lipoprotein （ HDL ） were respectively examined. The activities of malondialdehyde （ MDA ）, superoxide dismutase （ SOD ）, catalase （CAT） and glutathione peroxidase （GSH-PX） were measured. The left kidney was stained by HE for patho- logical examination. Results Compared with those in NC group and RL group,BG and LK/BW were signifi- cantly increased in rats of DN group and DN ＋ PB group（P 〈0.05）. The levels of BUN,Cr,24 h UMA, LDL, MDA were significantly increased （ P 〈 0.05 ） and the levels of SOD, CAT, SOD/MDA were significantly decreased（P 〈0.05） in rats of DN group,compared with those in NC group,RL group and DN ＋ PB group. And the parameters mentioned above were significantly i

关 键 词：糖尿病肾病 四氧嘧啶 普罗布考 氧化应激 

分 类 号：R285.5[医药卫生—中药学]