吡格列酮对糖尿病大鼠肾脏线粒体氧化应激的影响  

Influence of Pioglitazone on Renal Mitochondrial Oxidative Stress in Diabetic Rats

作　　者：杨前勇[1] 张静[2] 宋宁燕[1] 聂忠[1] 李刚[2] 

机构地区：[1]中国人民解放军第九四医院内分泌科,南昌330002 [2]中国人民解放军第九四医院药剂科,南昌330002

出　　处：《南昌大学学报（医学版）》2012年第10期1-3,7,共4页Journal of Nanchang University：Medical Sciences

基　　金：南京军区医药卫生课题重点项目(11z018)

摘　　要：目的研究吡格列酮对糖尿病大鼠肾脏线粒体氧化应激的影响。方法采用链脲菌素诱导糖尿病模型,按随机数字表法将40只大鼠分为正常对照组、正常对照治疗组、糖尿病组和糖尿病治疗组,每组10只。正常对照治疗组和糖尿病治疗组给予吡格列酮10mg·kg-1·d-1灌胃,正常对照组和糖尿病组给予等剂量溶媒灌胃。第10周末测定血糖、肾质量指数、24h尿蛋白定量;检测各组大鼠肾脏线粒体丙二醛(MDA)、一氧化氮(NO)含量和锰超氧化物岐化酶(Mn-SOD)、总一氧化氮合酶(T-NOS)活性。结果糖尿病治疗组与糖尿病组比较,血糖差异无统计学意义(P>0.05),但肾质量指数和24h尿蛋白定量明显降低(P<0.01)。与正常对照组比较,糖尿病组肾脏线粒体MDA、NO含量及T-NOS酶活性升高,Mn-SOD活性降低(P<0.05或P<0.01);与糖尿病组比较,糖尿病治疗组肾脏线粒体MDA、NO含量及T-NOS酶活性下降、Mn-SOD活性升高(P<0.05或P<0.01)。结论早期糖尿病肾病大鼠肾脏线粒体存在明显氧化应激反应,吡格列酮对糖尿病大鼠肾脏线粒体有一定的抗氧化作用,这可能是其不依赖降糖的肾脏保护作用机制之一。Objective To study the effects of pioglitazone on renal mitochondrial oxidative stress in diabetic rats. Methods Diabetes mellitus（DM） was experimentally induced by the injection of streptozotocin. Wistar rats were randomly divided into four groups.normal control group （NC group）,NC treated with pioglitazone group（NCT group）, DM group, and DM treated with pioglitazone group（DMT group）,with 10 rats in each group. Rats in NCT and DMT groups were treated with intragastric administration of pioglitazone（10 mg· kg^-1 ·d^-1） ,and rats in NC and DM groups were given the equivalent dose solvent gavage. At the end of 10 weeks of treatment, blood glucose,renal mass index and 24 hour urinary protein excretion were detected and levels of malondialdehyde（MDA）, nitric oxide（NO）, manganese superoxide dismutase （Mn-SOD） and total nitric oxide synthase（T-NOS） in renal mitochondria were measured. Results Compared with DM group, pioglitazone decreased levels of MDA,NO and T-NOS,renal mass index and 24 hour urina- ry protein excretion and increased Mn-SOD levels （P〈0.05 or P〈0.01）. Compared with NC group,MDA,NO and T-NOS levels increased and Mn-SOD levels decreased in DM group（P〈 0.05 or P〈0.01）. There was no significant difference in blood glucose levels between DM group and DMT group. Conclusion Diabetic rats have renal mitochondrial oxidative stress. Pioglitazone treatment can protect renal mitochondria from oxidative injury through a mechanism of independ- ent of its hypoglycemic effect.

关 键 词：吡格列酮 糖尿病肾病 线粒体 氧化应激 动物 实验 大鼠 

分 类 号：R-332[医药卫生]