在微量白蛋白尿前后应用氯沙坦治疗糖尿病肾病的实验研究  

Is it better for diabetic nephropathy treated with losartan before microalbuminuria than after

作　　者：柳刚[1] 关广聚[1] 傅余芹[1] 吴涛[1] 李学刚[1] 文蓉珠[1] 赵敬杰[2] 晋运玲[3] 

机构地区：[1]山东大学第二医院肾内科,山东济南250033 [2]山东大学第二医院分子生物学实验室,山东济南250033 [3]山东大学第二医院门诊部,山东济南250033

出　　处：《山东大学学报（医学版）》2006年第3期240-243,共4页Journal of Shandong University:Health Sciences

基　　金：国家教育部博士点基金资助项目(20030422068);山东省中医药管理局资助项目(200329105)

摘　　要：目的:观察在微量白蛋白尿发生前后应用氯沙坦对糖尿病肾病的治疗作用及其机制。方法:单侧肾切除的链脲佐菌素(STZ)糖尿病大鼠,随机分为糖尿病对照组、氯沙坦治疗1组和氯沙坦治疗2组。观测肾脏形态学及肾功能变化,并采用荧光实时定量RT-PCR检测肾脏转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制剂1(PAI-1)等细胞因子的表达情况。结果:糖尿病对照组大鼠尿微量白蛋白(UAER)持续上升;血肌酐(Scr)、肾脏肥大指数(KW/BW)、肾小球平均体积(MGV)、系膜面积比(FMA)以及肾脏TGF-β1、CTGF、PAI-1和纤维连接蛋白(FN)的mRNA表达均明显升高,而肌酐清除率(Ccr)已开始下降。氯沙坦治疗1组和2组以上指标均明显改善,且两组之间无显著差异。结论:氯沙坦可通过下调肾脏细胞因子基因表达,起到保护肾脏作用,但在微量白蛋白尿出现之前进行干预的效果并不比之后更好。Objective： To estimate the effect of losartan on diabetic nephropathy before or after microalbuminuria. Methods： Forty uninephrectomized male Wistar rats were divided into 4 groups at random： normal control （NC）, diabetic nephropathy control （DN）, early treatment with losartan（DL1） and late treatment with losartan （DL2）,and they were made diabetes by single intraperitoneal injection of streptozotocin （STZ, 60 mg/kg）. DL1 group was treated with losartan （20 mg· kg^- 1· d^- 1 ） for 8 weeks immediately, while DL2 group from the 9^th week. At the end of the 16^th week, all rats were sacrificed, and their left kidneys were removed and weighed. The mean glomerular volume （MGV） and the fractional mesangial area （FMA） were calculated by medical image analysis system. The mRNA expression of TGF-β1, CTGF, PAI-1 and FN were detected by quantitative real time RT-PCR. Urinary albumin excretion rate （UAER）, as well as serum creatinine （sCr） and creatinine clearance rate （Ccr） was detected.Results： （1）Compared with group NC, UAER increased by 1268% at the end of the 8^th week and 2192% at the end of the 16^th week in group DN; At the same time, Set in DN group elevated significantly （ 136% ）, and KW/BW, MGV and FMA in DN too （129%, 98% and 183% separately）. The mRNA expression of TGF-β1, CTGF, PAI-1 and FN in group DN increased by 2292%, 1342%, 2861% and 596% separately. Whereas all these indexs decreased in group DL1 and DL2 （ P 〈 0.05）, and there was no significant difference between group DL1 and DL2 （ P 〉0.05）; （2）However, Ccr in group DN began to decline at the end of the 16^th week （ 14.8%, P 〈0.05）, but it in group DL1 and DL2 was still higher than that in group NC （ P 〈 0.05） ; （3）FMA was negatively correlated with Ccr in group DN at the 16^th week. And the mRNA expression level of TGF-β1, CTGF, PAI-1 and FN was positively correlated with UAER, KW/BW, MGV and FMA. Conclusion：（1）The mRNA expression level of TGF-β1,

关 键 词：糖尿病肾病 转化生长因子 结缔组织 纤溶酶原激活物抑制物Ⅰ 氯沙坦 

分 类 号：R587.1[医药卫生—内分泌]