吡咯烷二硫代氨基甲酸酯对2型糖尿病大鼠大血管损伤的保护作用  

Protective effects of pyrrolidine dithiocarbamate on macroangiopathy in diabetic rats

作　　者：张玉娜[1] 朱铁年[2] 陈艳霞[3] 刘桂红[1] 刘建坤[2] 赵瑞景[4] 

机构地区：[1]河北医科大学第四医院内分泌科 [2]中国人民解放军白求恩国际和平医院肿瘤科 [3]河北医科大学第二医院内分泌科 [4]河北医科大学免疫学教研室,河北石家庄050017

出　　处：《中国老年学杂志》2011年第16期3077-3079,共3页Chinese Journal of Gerontology

基　　金：河北省自然科学基金资助项目(No.C2009001232);河北省科技支撑计划项目(No.10276105D-66);河北省卫生厅资助项目(No.20090168);国家人事部留学人员科技活动项目择优资助项目(2008)

摘　　要：目的观察吡咯烷二硫代氨基甲酸酯(PDTC)的降糖作用,以及对2型糖尿病(T2DM)大鼠主动脉血管内皮诱生型一氧化氮合酶(iNOS)表达及硝基酪氨酸(NT)生成的影响。方法雄性Wistar大鼠,随机分为两组,正常对照组(NC组)和高脂饮食组(HFD组),喂养8 w后,HFD组腹腔注射小剂量链脲佐菌素(STZ),诱导成功的T2DM大鼠随机分为糖尿病组(DM组)和PDTC治疗组(PDTC组),PDTC治疗组接受PDTC(50 mg/kg)治疗,持续1周,断头处死后留取血浆检测血糖及各种生化指标;留取主动脉组织,检测主动脉组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的含量;HE染色观察主动脉组织形态学变化,免疫组化观察各组大鼠主动脉内皮iNOS、NT的表达。结果 PDTC治疗1w后,PDTC组大鼠空腹血糖、MDA水平明显低于DM组;SOD和GSH-Px水平明显高于DM组(P<0.01)。免疫组化结果显示:iNOS、NT在DM组大鼠主动脉内皮表达水平明显高于NC组;在PDTC治疗组大鼠主动脉内皮表达水平明显低于DM组。结论 PDTC不仅具有降血糖作用,而且可以减少iNOS的表达,进而减少过氧亚硝基阴离子(ONOO-)及NT的产生,延缓了糖尿病大血管并发症的发生。早期应用PDTC可预防T2DM因"代谢记忆"所致的大血管损伤。Objective To examine the effects of pyrrolidine dithiocarbamate（PDTC）on reducing blood glucose levels and production of iNOS and NT in type 2 diabetic（T2DM） rats induced by long-term high-fat feeding accompanied with intraperitoneal injection of streptozotocin（STZ）.Methods Male Wistar rats were divided randomly into 2 groups：normal control（NC group） and high-fat diet groupS（HFD group）.After 8 weeks,STZ was administered via intraperitoneal injection to make model in HFD group.Then the T2DM rats were further divided randomly into 2 groups：T2DM（DM group） and PDTC-treated groups（PDTC group）,PDTC group was administered PDTC（50 mg/kg） via intraperitoneal injection.After treatment for 1 week,blood and the vascular tissues were taken from rats.Blood glucose levels were estimated again.Malondialdehyde（MDA）,superoxide dismutases（SOD） and glutathione peroxidase（GSH-Px） concentrations were determined in aortic tissue by the use of commercial kits.The pathological morphological changes and the expression of iNOS and NT were observed by HE staining and immunohistochemistry.Results After treatment with PDTC,the fasting blood glucose and MDA concentration were significantly lower than that of DM group,while the SOD and GSH-Px concentrations were higher in PDTC group when compared with the DM group（P0.01）.Expression of iNOS,NT in aortic endothelium were significantly higher in DM group than those in NC group,the production of iNOS and NT were reduced after administration of PDTC.Conclusions PDTC can reduce blood glucose levels,attenuate production of iNOS and ONOO-in aortic endothelium and delay macroangiopathy in diabetic rats.So early application of PDTC can prevent diabetic macroangiopathy from ＂metabolic memory＂.

关 键 词：T2DM 氧化应激 吡咯烷二硫代氨基甲酸酯 诱生型一氧化氮合酶 硝基酪氨酸 

分 类 号：R587.1[医药卫生—内分泌]