依布硒啉对db/db小鼠蛋白尿作用及其机制

目的探讨依布硒啉（ebselen）对db/db小鼠蛋白尿的作用及其可能机制。方法 16只8周龄db/db小鼠随机分为依布硒啉组8只（Ebs组）和糖尿病肾病组8只（DN组）,分别给予依布硒啉50mg/kg和生理盐水灌胃,2次/d;8只8周龄db/m小鼠为非糖尿病对照组（对照组）,给予生理盐水灌胃,2次/d;每周监测各组体质量、空腹血糖。8周后检测24h尿白蛋白、尿8-羟基脱氧鸟苷酸、肾脏组织丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性。结果治疗8周后,DN组空腹血糖（（31.9±2.4）mmol/L）、24h尿白蛋白（（240.7±26.3）μg/24h）、尿8-羟基脱氧鸟苷酸（183.5±26.7）ng/24h）、肾组织匀浆丙二醛含量（（11.5±2.2）nmol/mg）明显高于对照组（（6.7±0.8）mmol/L、（16.4±1.1）μg/24h、（74.8±13.5）ng/24h、（3.6±0.9）nmol/mg）和Ebs组（（21.3±1.1）mmol/L、（76.3±14.7）μg/24h、（86.9±16.5）ng/24h、（7.7±1.6）nmol/mg）,肾脏组织超氧化物歧化酶和谷胱甘肽过氧化物酶活性（（312.4±16.9）、（167.2±14.8）u/mg）明显低于对照组（（358.2±13.4）、（217.4±15.7）u/mg）和Ebs组（（366.5±24.7）、（191.2±16.5）u/mg）（P〈0.01）;Ebs组空腹血糖、24h尿白蛋白和肾组织丙二醛含量高于对照组（P〈0.01）,尿8-羟基脱氧鸟苷酸水平、超氧化物歧化酶和谷胱甘肽过氧化物酶活性与对照组比较差异无统计学意义（P〉0.05）。结论依布硒啉能降低蛋白尿,其机制可能与减轻db/db小鼠肾脏组织氧化应激有关。

Effect of ebselen on albuminuria in db/db mice and its mechanism

Objective To explore the effect of ebselen on albuminuria in db/db mice and its mechanism.Methods Sixteen 8-week-old db/db mice were divided into ebselen group and diabetic nephropathy（DN）group,with 8mice in each group.Ebselen group received lavage with ebselen and DN group received lavage with normal saline,twice a day.Another 8age-matched non-diabetic littermates db/m mice（control group）were treated with normal saline by lavage twice a day.The body mass and fast plasma glucose were measured every week.The levels of 24-hour urinary albumin,8-hydroxydeoxyguanosine（8-OHdG）,maleic dialdehyde（MDA）,the activity of superoxide dismutase（SOD）and glutathione peroxidase（GSH-Px）in kidney tissue were detected after 8-week treatment.Results After 8-week treatment,the levels of fasting plasma glucose（（31.9±2.4）mmol/L）,24-hour urinary albumin（（240.7±26.3）μg/24h）,8-OHdG（183.5±26.7）ng/24h）and MDA（（11.5±2.2）nmol/mg）in DN group were higher than those in control group（（6.7±0.8）mmol/L,（16.4±1.1）μg/24 h,（74.8±13.5）ng/24 h,（3.6±0.9）nmol/mg）and ebselen group（（21.3±1.1）mmol/L,（76.3±14.7）μg/24 h,（86.9±16.5）ng/24 h,（7.7±1.6）nmol/mg）,and the activities of SOD and GSH-Px were significantly lower in DN group（（312.4±16.9）,（167.2±14.8）u/mg）than those in control group（（358.2±13.4）,（217.4±15.7）u/mg）and ebselen group（（366.5±24.7）,（191.2±16.5）u/mg）（P〈0.01）.The levels of fasting plasma glucose,24-hour urinary albumin level and MDA were higher in ebselen group than those in control group（P〈0.01）,and there were no significant differences in 8-OHdG level,and the activities of SOD and GSHPx between two groups（P〉0.05）.Conclusion Ebselen can reduce albuminuria,and the mechanism may be correlated with the inhibition of oxidative stress.