吡咯烷二硫代氨基甲酸酯及吡格列酮保护糖尿病大鼠肾脏机制的实验研究  

Protective Mechanism of Pyrrolidine Dithiocarbamate and Pioglitazone on Diabetic Rat Kidneys:An Experimeatal Study

作　　者：陈文钰[1] 徐向进[2] 陈频[2] 王艳桥[2] 

机构地区：[1]福建医科大学福总临床医学院,福建福州350025 [2]南京军区福州总医院内分泌科,福建福州350025

出　　处：《中国现代医生》2010年第11期1-4,42,共5页China Modern Doctor

摘　　要：目的探讨吡咯烷二硫代氨基甲酸酯(PDTC)及吡格列酮(PIO)对糖尿病大鼠肾脏保护作用及机制。方法链脲佐菌素(STZ)诱导糖尿病模型组大鼠40只,随机分为糖尿病未治疗组(DM组),PDTC治疗组(P组),吡格列酮治疗组(PIO组)和PDTC联合PIO治疗组(P+P组),正常大鼠作为对照组(NC组)。8周后测定血糖、血尿素氮(BUN)、肌酐(Scr)、24h尿蛋白(24hUP)及肾重指数(KI);银染观察肾病理改变及免疫印迹测定肾脏NF-κBp65、MCP-1表达。结果①与NC组比,DM组及各治疗组KI、血糖、BUN、Scr、24hUP、ECM堆积指数及NF-κBp65和MCP-1表达均明显增加,体重显著减轻(均P<0.01);②与DM组比,各治疗组KI、血糖、BUN、Scr、24hUP、ECM堆积指数均明显降低,体重显著增加(均P<0.05或P<0.01);NF-κBp65、MCP-1表达明显降低并与肾病理及功能改变呈正相关(P<0.01);③与P组、PIO组比较,P+P组上述指标改善更明显,NF-κBp65和MCP-1表达进一步下降,肾病理及功能改善更明显(除了P+P组血糖与PIO组比,P>0.05,余均P<0.01;)。结论糖尿病大鼠肾组织NF-κBp65和MCP-1表达明显增加,PDTC和PIO对DM大鼠肾脏均有保护作用;二者联用较单药效果更好,其机制可能与抑制NF-κB活性,下调MCP-1表达有关。Objective To investigate the protective effects of pyrrolidine dithiocarbamate（PDTC） and pioglitazone（PIO） on the diabetic rat kidneys and possible mechanism. Methods Forty streptozotocin-induced diabetic rats were randomly divided into 4 groups： diabetic rats without treatment（DM group）, diabetic rats treated with PDTC （P group ）, diabetic rats treated with PIO（PIO group）, diabetic rats treated with combined PDTC and PIO（P＋P group）,and normal rats were used as control group（NC group）. Fasting plasma glucose（FPG）,blood urea nitrogen（ BUN ）, serum creatinine（Scr）, 24h urinary protein（24hUP）and kidneys weight/body weight ratio（ KI ）were detected after 8 - week treatment. The pathological changes of the kidneys were observed by PASM and the expression of nuclear transcription factor-κB P65（NF-κB P65 ）and monocyte chemoattractant protein-1 （MCP-1） in the kidneys was studied by using western-blot. Results （1）Compared with group NC, the levels of KI, PG, BUN, Scr, 24hUP, extracellular matrix（ECM）accumulation index and the expression of NF- κB P65 and MCP-1 were significantly increased, but the body weight was greatly lowered in D, P, PIO and P＋P groups （all P〈0.01 ）. （2）Compared with group D, the levels of KI, FPG,BUN,Scr,24hUP, ECM accumulation index and the expression of NF-κB P65 and MCP-1 were significantly decreased in the three treated groups, but the body weight was greatly increased（P〈O.05 or P〈0.01 ）. The expression of NF- κB P65 and MCP-1 was positively related to the changes of renal pathology and function（P〈0.0l ）. （3）Compared with group P and group PIO,the above indexes of group P＋P were significantly improved（P〈0.01 ）,and the expression of NF-κB P65 and MCP-1 was obviously decreased with further improvement of renal pathological and functional changes（P〈0.01, except for group P＋P glucose vs group PIO P〉0.05 ）. Conclusion The expression of NF- κB P65 and MCP-1 in the renal tissue of di

关 键 词：糖尿病肾病 吡咯烷二硫代氨基甲酸酯 吡格列酮 核转录因子-ΚB 单核细胞趋化蛋白-1 

分 类 号：R587.1[医药卫生—内分泌]