氯沙坦对大鼠糖尿病肾损害的保护作用  

Renoprotection of diabetic rats with losartan

作　　者：叶山东[1] 陈燕[1] 王迎新[2] 李远思[1] 陈柯[3] 胡闻[3] 

机构地区：[1]安徽省立医院内分泌科,合肥230001 [2]安徽医学高等专科学校,合肥230061 [3]安徽省立医院病理科,合肥230001

出　　处：《中国新药杂志》2007年第8期610-613,共4页Chinese Journal of New Drugs

基　　金：安徽省自然科学基金资助课题(01041181)

摘　　要：目的:探讨血管紧张素Ⅱ受体阻滞剂氯沙坦对糖尿病肾损害的保护作用与机制。方法:36只大鼠分成正常对照组、糖尿病模型组和氯沙坦治疗组,每组12只。模型组和氯沙坦组腹腔注射链脲佐菌素65 mg.kg-1建立糖尿病模型,在模型建立1周后氯沙坦组灌胃给予氯沙坦5 mg.kg-1.d-1,共12周。检测各组第1,4,12周血糖、24 h尿视黄醇结合蛋白(RBP)、尿白蛋白(A lb)排泄率;分别于第4和12周每组各处死5只大鼠,取肾,称重,计算肾脏肥大指数;分离肾皮髓质,荧光定量RT-PCR法检测皮质转化生长因子β1(TGFβ1)mRNA水平;透视电子显微镜检查肾小球基底膜、系膜区的病理改变。结果:第4和12周时模型组尿Alb,RBP排泄、肾脏肥大指数和TGFβ1mRNA表达量均显著高于正常对照组(P<0.01),氯沙坦组的这些指标则较模型组明显减少(P<0.01)。电镜显示模型组肾小球毛细血管基底膜增厚,系膜和系膜细胞增生;氯沙坦组肾小球毛细血管基底膜也有不规则增厚,较同时期模型组减轻。结论:氯沙坦对糖尿病肾损害有确切的保护作用,其机制可能部分与氯沙坦抑制肾脏TGFβ1过度表达有关。Objective ： To study the renoprotective effect and mechanism of angiotensin II receptor blocker （ARB）-losartan in diabetic rats. Methods： Thirty-six rats were randomly assigned into three groups： healthy control （n = 12）, diabetic control （n=12）, or losartan administration （n=12）. The diabetic model of rats were set up by subabdominal injection with strephtozotocin 65 mg.kg^-1. After one week post the diabetic model, the rats were fed with losartan 5 mg.kg^-1.d^-1 for 12 weeks. Levels of blood glucose and excretion rates of urinary albumin and retinal-binding protein （RBP） were analyzed at the end of the 1 st-, 4 th- and 12 th-week administration of losartan. The rats were sacrificed to collect re- nal tissues for the measurement of renal hyperplasia index by weighing and the expressions of TGFβ1, mR- NA in the renal cortex by a fluorescent RT-PCT assay at the end of the 4 th- and 12 th week administra- tion of losartan. The histopathological examinations on the glomerular basement membrane and the mesan- gium of diabetic rats were conducted by electron microscopy at the end of the 4 th- and 12 th-week admin- istration of losartan. Results： Compared with the healthy control rats, the excretion rates of urinary albu- min and RBP, the renal hyperplasia index and expression of TGFβ1, mRNA were significantly escalated in diabetic rats at the end of the 4 th and 12 th week （P 〈0.01 ）. The losartan-treated rats showed signifi- cant improvements of those episodic focal signs and indexes compared with the diabetic rats （P 〈 0.01 ）. The electron microscopy showed that the losartan-treated rats had less hyperplasia of glomerular basement membrane and mesangium than the diabetic rats. Conclusion： Losartan prevented rats from diabetic ne- phropahty by down-regulating TGFβ1, mRNA expression in renal tissue.

关 键 词：氯沙坦 糖尿病肾病 转化生长因子B 

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