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.
出处
《中国实验动物学报》
CAS
CSCD
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
关键词
替米沙坦
基因芯片
糖尿病
肾脏功能
Telmisartan
Diabetes mellitus
Rats
Gene microarray
Kidney function
