曲尼司特对马兜铃酸肾病大鼠TGFβ1/Smad-6、BMP-7的影响  

EFFECT OF TRANILAST ON TGFΒ1/SMAD -6, BMP-7 OF RATS WITH ARISTOLOCHIC ACID NEPHROPATHY

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内科,成都610041

出　　处：《现代预防医学》2009年第1期175-177,179,共4页Modern Preventive 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.d,模型组、曲尼司特治疗组及安博维组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(Crea)、转化生长因子β1(TGFβ1)和原位杂交Smad-6、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TGFβ1,上调Smad-6、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TGFβ1,上调Smad-6、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] 24 rats were randomly divided into 4 groups： normal control group, model group, irbesartan treatment group, tranilast treatment group. The rats in model and treatment groups received 20mg/kg.d AA contained in the water extract of Aristolochica manshuriensis Kom by gastric tube for 5 days in the 1st week. and later 15mg/kg.d for 7 days in every other week up to llth week. Rats in model group received sodium carboxymethycellulose via gavage. Rats in irbesartan treatment group received irbesartan lOmg/kg/d via gavage. Rats in tranilast treatment group received tranilast 400 mg/kg via gavage. Rats were sacrificed at the end of 12th week. The body weight, hemoglobin, Scr were measured at the end of the study. Renal pathologieal changes were evaluated and imnmnohistochemistry was used to examine the expression of TGFβ1 . 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 were significantly increased （P 〈 0.05） and Ser of rats treated with tranilast were significantly reduced （P 〈 0.05） ; （2） Tranilast attenuated tubular cells vaeuolations as well as interstitial fibrosis. （3） Meanwhile, tranilast down-regulated the protein of TGF-β1, up-regulated the mRNA of BMP-7 and Smad6 in kidney. [Conclusion] Tranilast has a renoprotective effect on aristoloehie acid nephropathy in rats. The mechanism may be relative with that tranilast can decrease the expression of TGF-β1, increase the expression of BMP-7 and Smad6 in the kidney. And tranilast inhibits the transdi.fferentation of renal primary ceils, regulates the synthesis and degradation system of extraeeilular matrix.

关 键 词：曲尼司特 马兜铃酸肾病 转化生长因子β1 Smad-6 骨成形蛋白7 

分 类 号：R97[医药卫生—药品]