曲尼司特对马兜铃酸肾病大鼠肾纤维化防治作用的初步研究  

Prevention of aristolochic acid nephropathy in rats with tranilast

作　　者：李聃丹[1] 吴欣[1] 陶冶[1] 刘其锋[1] 薄虹[1] 王雪荣[1] 

机构地区：[1]四川大学华西医院肾脏内科,成都610041

出　　处：《重庆医学》2008年第12期1309-1311,共3页Chongqing medicine

摘　　要：目的观察曲尼司特干预治疗对马兜铃酸肾病大鼠肾纤维化防治作用,以探讨其可能的机制。方法雄性SD大鼠24只,随机分为4组。对照组予灌服饮用水10mL.kg-1.d-1,模型组、曲尼司特治疗组及安博维治疗组均予关木通水煎剂灌胃共12周建立马兜铃酸肾病模型。12周时观察各组大鼠血红蛋白(Hb)、肌酐(Cr)、转化生长因子β1(TGF-β1)、肝细胞生长因子(HGF)和原位杂交骨成形蛋白7(BMP-7)的表达。结果曲尼司特能延缓血红蛋白降低及血清肌酐(Scr)上升;减轻肾小管上皮细胞空泡变性、小管萎缩及间质纤维化;曲尼司特能下调马兜铃酸肾病大鼠肾组织中的TGF-β1,上调HGF、BMP-7的表达。结论曲尼司特可能通过下调马兜铃酸肾病大鼠肾组织中TGF-β1,上调HGF、BMP-7的表达以抑制肾小管上皮细胞表型转分化,从而减轻肾纤维化,发挥其肾脏保护作用。Objective To investigate the effects and mechanism of tranilast on aristolochic acid nephropathy in rats. Methods Twenty four rats were randomly divided into 4 groups：normal control group, model group,irbesartan treatment group and tranilast treatment group. The rats in model and treatment groups received 20mg·kg^-1·d^-1 AA contained in the water extract of aristolochica manshuriensis Kom by gastric tube for 5d in the 1st week,and later 15mg·kg^-1·d ^-1 for 7d in everry other week up to 11 week. Rats in model group received sodium carboxymethycellulose via gavage. Rats in irbesartan treatment group received irbesartan 10mg·kg^-1·d^-1 via gavage. Rats in tranilast treatment group received tranilast 400 mg/kg via gavage. Rats were sacrificed at the end of 12 week. The body weight,hemoglobin,Scr were measured at the end of the study. Renal pathological changes were evaluated and immunohistochemistry was uesed to examine the expression of TGF-β1. In situ hybridization was used to measure the expression of Smad-6,BMP-7 mRNA in the kidney. Results （1）Compared with the model rats,hemoglobin of rats treated with tranilast was significantly increased（P〈0.05） and Scr of rats treated with tranilast was significantly reduced（P〈0.05）. （2）On histopathology tranilast attenuated tubular cells vacuolations as well as interstitial fibrosis. （3）Meanwhile, tranilast down-regulated the protein of TGF-β1, up-regulated the protein of HGF and the mRNA of BMP-7 in kidney. Conclusion Tranilast has a renoprotective effect on aristolochic acid nephropathy in rats. The mechanism may be that tranilast can decrease the expression of TGF-β1 ,increase the expression of BMP-7 and HGF in the kidney. And tranilast inhibites the transdifferentation of renal primary cells, regulates the synthesis and degradation system of extracellular matrix.

关 键 词：曲尼司特 马兜铃酸肾病 转化生长因子β1 肝细胞生长因子 骨成形蛋白7 

分 类 号：R692[医药卫生—泌尿科学]