曲尼司特对马兜铃酸肾病大鼠肾脏TGFβ_1、FN的影响

Experimental study of protective effect of tranilast on aristolochic acid nephropathy in rats

目的:观察曲尼司特干预治疗对马兜铃酸肾病大鼠肾脏保护作用,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)及肾脏病理的影响。应用免疫组化方法测定肾组织TGFβ1和FN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和FN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和FN的表达以抑制肾小管上皮细胞表型转分化,调节细胞外基质的生成与降解,从而减轻肾脏病理损害,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 The 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 20 mg. kg. d-1 AA contained in the water extract of Aristolochica manshuriensis Kom by gastric tube for 5 days in the 1st week, and later 15 mg.kg.d t for 7 days in every other week up to llth week. Rats in model group received sodium carboxymethycellulose via garage. Rats in irbesartan treatment group received irbesartan 10 mg.kg.d-1 via gavage. Rats in tranilast treatment group received tranilast 400 rag. kg via garage. Rats were sacrificed at the end of weekl2. The body weight, hemoglobin, Scr were measured at the end of the stud- y. Renal pathological changes were evaluated and immunohistochemistry was uesed to examine the expression of TGFβ1 and FN in the kidney. RESULTS （1） Compared with the model rats, hemoglobin of rats treated with tranilast significantly increased （P〈0. 05） and Scr of rats treated with tranilast significantly reduced（P〈0. 05） ; （2） On histopathology tranilast attenuated tubular cells vaeuolations as well as interstitial fibrosis. （3） Meanwhile, immunohistochemstry analysis showed tranilast could decrease the expression of TGFβ1 and FN in the kidney of rats with aristolochie acid nephropathy. CONCLUSION Tranilast has a renoprotective effect on aristoloehie acid nephropathy in rats. The mechanism may be related to that tranilast can decrease the expression of TGFβ1 and FIN in the kidney. And tranilast inhibits the transdifferentation of renal primary cells, regulate the syn- thesis and degradation system of extracellular matrix.