替米沙坦改善糖尿病大鼠肾脏功能机制研究  

Modulation mechanism of kidney function by telmisartan in diabetic rats

作　　者：张茜[1] 肖新华[1] 黎明[1] 李文慧[1] 李伟[1] 于淼[1] 张化冰[1] 平凡[1] 孙晓方[1] 茅李莉[1] 杨国华[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科卫生部内分泌重点实验室,北京100730

出　　处：《中国实验动物学报》2012年第6期10-14,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：北京协和医院基金项目(编号:2006119);国家临床重点专科建设项目

摘　　要：目的研究替米沙坦对糖尿病大鼠24 h尿蛋白、血肌酐、肌酐清除率(Ccr)和血清尿素氮(BUN)等相关代谢指标的影响,且应用基因芯片探讨替米沙坦改善肾功能的机制。方法 30只SD大鼠,其中随机选取10只为正常对照组(给予等体积生理盐水)。选用20只大鼠,采用STZ法制备糖尿病模型,而后将16只造模成功的糖尿病大鼠随机分为替米沙坦治疗组(给予10 mg/kg/d的替米沙坦,n=8)和糖尿病模型组(给予等体积生理盐水,n=8)。三组大鼠均连续灌胃12周。每4周测定大鼠空腹血糖(FBG)和体重。12周末测定大鼠24h尿蛋白、尿肌酐、血肌酐和BUN水平。12周末处死大鼠,取肾脏组织进行基因芯片实验,并运用real time PCR进行验证。结果糖尿病模型组24h尿蛋白(P<0.01)、血肌酐(P<0.05)和BUN(P<0.01)比对照组显著升高,Ccr较对照组显著降低(P<0.05)。替米沙坦能改善糖尿病大鼠24h尿蛋白、血肌酐、Ccr和BUN水平。基因芯片结果显示替米沙坦组较糖尿病模型组有1541个基因发生显著改变,其中554个上调,987个下调。基因富集分析显示这些差异表达基因集中在氧化磷酸化通路和PPAR通路。Real time PCR证实替米沙坦组较糖尿病模型组ATP合成酶β亚基(Atp5b)、细胞色素c氧化酶亚基VIc(Cox6c)和NADH脱氢酶(辅酶Q)铁硫蛋白3(Ndufs3)基因显著下调。结论替米沙坦能有效改善糖尿病大鼠肾脏功能。替米沙坦的肾脏改善作用可能是通过线粒体氧化磷酸化通路和PPAR-γ通路调节。Objective To explore the effects of telmisartan on the kidney function in diabetic rats and to inves- tigate its possible mechanism. Methods SD rats were randomly divided into two groups： diabetic group （ n = 20） and control group （n = 10）. The diabetic group was injected with streptozotoein （STZ）. Diabetic rats were randomly divided into two groups： telmisartan group （treated with 10 mg./kg/d telmisartan, n = 8） and diabetic group （n = 8）. The fasting blood glucose, body weight, 24-hour urinary protein, creatinine clearance rate （Ccr） , serum creatinine and blood urea ni- trogen （BUN） were tested. Gene expression in the rat renal tissues was assyed with microarray analysis. Results Telmis- arran significantly decreased 24-hour urinary albumin （ P 〈 0.01 ） , serum creatinine （ P 〈 0. 05 ） , BUN （ P 〈 0.01 ） , and increased Ccr （ P 〈 0. 05 ） , compared with those of the diabetic group. Microarray analysis showed that expressions of 1541 genes were significantly changed in the telmisartan group （554 increased, 987 decreased）. Real-time PCR verified that ATP synthase beta subunit （ATP5b）, eytoehrome c oxidase subunit Vic （Cox6c）, and NADH dehydrogenase （ubiqui- none） Fe-S protein 3 （Ndufs3） were significantly down-regulated. Conclusion Telmisartan can improve kidney functionin diabetic rats. Mitochondria oxidative phosphorylation and PPAR-Y/pathway may be involved in the mechanism of action.

关 键 词：替米沙坦 基因芯片 糖尿病 肾脏功能 

分 类 号：Q95-33[生物学—动物学]