氯沙坦对局灶节段性肾小球硬化大鼠转化生长因子-β_1及结缔组织生长因子的影响  

Influence of Losartan on Transforming Growth Factor-β_1 and Connective Tissue Growth Factor in Rats with Focal Segmental Glomerulosclerosis

作　　者：邹敏书[1] 余健[1] 刘雪梅[1] 聂国明 刘静[1] 

机构地区：[1]广州军区武汉总医院儿科,武汉430070

出　　处：《中国药师》2008年第1期37-39,共3页China Pharmacist

摘　　要：目的:探讨局灶节段性肾小球硬化(FSGS)大鼠转化生长因子-β_1(TGF-β_1),结缔组织生长因子(CTGF)在肾组织中的表达,检测尿液中两者的水平。观察氯沙坦对肾组织TGF-β_1、CTGF蛋白的表达及尿液两者水平的影响。方法:40只Wist- ar大鼠随机分为实验组和治疗组。采用单侧肾摘除后重复静脉注射多柔比星(ADR)制作加速FSGS大鼠动物模型。第1次注药后1周,治疗组大鼠给予氯沙坦50mg·kg^(-1)·d^(-1)灌胃,实验时间12周。于第6,12周免疫组化观察肾组织TGF-β_1、CTGF蛋白质的表达,EIISA检测尿液中两者水平。结果:与治疗组相比,实验组12周时尿液TGF-β_1、CTGF水平,肾组织内TGF-β_1、CTGF蛋白质的表达明显升高(P<0.01)。肾组织内TGF-β_1蛋白与CTGF蛋白的表达显著正相关(r=0.83,P<0.01),尿液中两者排泄量亦明显正相关(r=0.74,P<0.01)。结论:FSGS大鼠TGF-β_1、CTGF蛋白在肾组织表达及尿液中的排泄明显升高。氯沙坦可减轻肾组织TGF-β_1、CTGF蛋白的表达,减少两者尿液中的排泄而有肾保护作用。Objective： To investigate the protein expression of transforming growth factor-β1 （ TGF-β1 ） and connective tissue growth factor（CTGF） ,detect：the level of urinary TGF-β1 and CTGF in rats with focal segmental glomerulosclerosis （FSGS）. To observe the influence of losartan on the expression of the two proteins in renal tissue and the excretion in urine. Method： The experiments were performed on 40 male rats. The rats were randomly divided into two groups （FSGS experimental group, losartan treated group）. All rats were treated by repeated intravenous injection of adriamyein（ADR） after the half nephrectomy to make accelerating FSGS rats model. Treated group received the losartan 50 mg·kg^-1 ·d^-1 by gastric perfusion one week after the first injection of ADR until the end of the study. The final study was finished at week 12. The proteins expression of TGF-β1 and CTGF in kidney tissue were detected by immunohistochemical staining, urinary TGF-β1 and CTGF were assayed by enzyme-linked immunosorbent assay （ELISA） at 6-12 week respectively. Result： Compared with treated group at 12 weeks, urinary TGF-β1 ,CTGF excretion, the protein expression of TGF-β1 ,CTGF were significantly increased in the experimental group（ P〈0.01 ）. A significant positive correlation was observed between the protein expression of TGF-β1 and CTGF in renal tissue（r=0.83, P〈0.01 ）, and the excretion of TGF-β1 and CTGF in urine also （ r=0.74, P〈0.01 ）. Conclusion： The protein expression of TGF-β1, CTGF was significantly increased in rats with FSGS. The increased urinary excretion of TGF-β1 and CTGF were also observed. Losartan could down-regulation the protein expression of TGF-β1 and CTGF in kidney tissue,decrease the excretion of the two to protect kidney.

关 键 词：氯沙坦 局灶节段性肾小球硬化 转化生长因子-β1 结缔组织生长因子 

分 类 号：R965.1[医药卫生—药理学]