氯沙坦对糖尿病大鼠肾脏的保护作用  

Protective effect of losartan on kidney of diabetic rats

作　　者：李小彦[1] 武文明[2] 栗俊杰[3] 廖飞[1] 陈全[4] 

机构地区：[1]重庆医科大学药学院,重庆400016 [2]重庆医科大学基础医学院生物化学与分子生物学教研室,重庆400016 [3]重庆医科大学基础医学院病原生物学教研室,重庆400016 [4]重庆医科大学基础医学院免疫学教研室,重庆400016

出　　处：《药学服务与研究》2008年第3期204-208,共5页Pharmaceutical Care and Research

摘　　要：目的:观察氯沙坦对糖尿病(diabetes mellitus,DM)大鼠肾脏病变的保护作用及其机制。方法:采用链脲霉素诱导SD大鼠造模,大鼠分为3组:正常对照组、DM模型组和氯沙坦治疗组。12周末时,采用HPLC-荧光分析法测定血浆同型半胱氨酸(homocysteine,Hcy)含量;常规方法检测各组大鼠肾重/体重、血糖、尿素氮、血肌酐、尿白蛋白排泄率;放射免疫法检测肾组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)含量;免疫组化法检测肾组织结缔组织生长因子(connective tissue growth fac-tor,CTGF)表达;透射电镜观察肾脏超微结构。结果:12周末时,DM模型组大鼠血浆Hcy的含量明显增加,肾皮质CTGF表达显著升高,肾组织AngⅡ含量显著增多,肾重/体重、血糖、尿白蛋白排泄率、尿素氮、血肌酐显著增高,肾脏超微结构改变明显。氯沙坦治疗组上述指标显著低于DM模型组(P<0.01),肾脏超微结构改变明显较轻。结论:氯沙坦对DM大鼠肾脏形态和功能有明显保护作用,其机制值得进一步研究。Objective： To observe the protective effects of losartan against renal lesion in diabetes mellitus of rats. Methods： The diabetes mellitus Sprague Dawley rats was induced by streptozotocin. The diabetic rats were randomly divided into three groups：normal control group, diabetic model group and losartan treatment group, At the end of the 12th week, the plasma concentration of homocysteine（Hcy） was detected by HPLC method. The mass index of kidney, blood sugar, urea nitrogen, serum creatinine and urinary albumin excretion rate（UAER） were detected by convintional methods. Angiotensin Ⅱ （AngⅡ） in renal tissue was detected by radioimmunoelectrophoresis, Connective tissue growth factor （CTGF） in renal tissue was detected by immunohistochemical method and uhrastructure of kidney was observed under transmission electron microscope. Results： At the end of the 12th week, the plasma concentration of Hey,the expression of CTGF in renal cortex, the blood sugar, UAER, urea nitrogen, serum creatinine, mass index of kidney and Ang Ⅱ were significantly increased in diabetic model rats, and the ultrastrueture of kidney was noticeably changed. The above indexes in losartan treatment group were significantly lower than those in diabetic model group （P〈0.01）, and changes of kidney uhrastructure were improved. Conclusion： Losartan can reduce diabetic nephropathy through reducing plasma concentration of Hcy, decreasing the level of Ang Ⅱ in the renal tissue,and down regulating the expression of CTGF. In other words, losartan has obvious protective effects on morphology and function of diabetic rats. So it is worthy of further study.

关 键 词：糖尿病肾病 氯沙坦 结缔组织生长因子 血管紧张素Ⅱ 大鼠 

分 类 号：R965.1[医药卫生—药理学] R587.24[医药卫生—药学]