曲尼司特对CsA慢性肾毒性大鼠TGF-β/Smad通路的影响  

Effects of tranilast on TGF-β/Smad pathways in rats with chronic cyclosporine A nephrotoxicity

作　　者：胡丽娟[1] 李莎莎[1] 陶冶[2] 刘其锋[2] 章崇杰[1] 吴欣[2] 李聃丹[2] 罗志娟[1] 

机构地区：[1]四川大学,华西基础与法医学院免疫教研室 [2]四川大学,华西医院肾脏内科

出　　处：《免疫学杂志》2009年第3期297-300,共4页Immunological Journal

基　　金：四川大学青年科学研究基金(校青06074)

摘　　要：目的探讨不同剂量曲尼司特(TNL)对环孢素A(CsA)慢性肾毒性大鼠肾脏TGF-β/Smad通路的的影响。方法雄性SD大鼠34只,随机分成正常对照组、模型组、TNL低剂量治疗组、TNL中剂量治疗组、TNL高剂量治疗组、安博维治疗组。采用低盐饮食加CsA20mg/(kg·d)灌胃的方法建立环孢素A慢性肾毒性大鼠模型。用RT-PCR和免疫组织化学检测不同剂量TNL对大鼠肾脏TGF-β1、Smad3、Smad7的影响。结果TNL能下调CsA慢性肾毒性大鼠肾组织中TGF-β1、Smad3的mRNA水平及在肾脏的表达,上调Smad7的mRNA水平及在肾脏的表达。结论在CsA慢性肾毒性大鼠模型中,TNL可能通过调节TGF-β/Smad通路而发挥抗纤维化的作用,从而减缓CsA慢性肾毒性的进展。Objective To investigate the effects of tranilast on TGF-β/Smad pathways in rats with chronic cyclosporine A nephrotoxicity. Methods Total of 34 SD rats were randomly divided into 6 groups:normal control group (N) received olive oil only by gavage; model control group (M) received CsA 20 mg/(kg·d) by gavage; Low (T1),median (T2) and high (T4)-dose group of tranilast treatment were given CsA 20 mg/(kg·d) and tranilast 100,200 and 400 mg/(kg·d) by gavage,respectively; Irbesartan treatment group (A) were given CsA 20 mg/(kg·d) and irbesartan 10 mg/(kg·d) by gavage. All rats were on low salt diet for 5 weeks,and kidneys were harvested at the end of the 4th week. TGF-β1,Smad3,and Smad7 were detected by semi-quantitative RT-PCR and immunohistochemistry.Results Morphologically,kidneys in group M exhibited significantly more fibrosis,which was blunted by tranilast. Either semi-quantitative RT-PCR or immunohistochemistry showed the expressions of TGF-β1 and Smad3 of the kidneys in group M were significantly higher than those in group N. Tranilast decreased the levels of TGF-β1 and Smad3,while increased the levels of Smad7 dose-dependently. High dose Tranilast displayed similar effects with irbesartan. Conclusion Tranilast shows a renal protective effect against chronic CsA nephrotoxicity in rat model by decreasing the levels of TGF-β1 and Smad3 and increasing the level of Smad7.

关 键 词：曲尼司特 环孢素A慢性肾毒性 转化生长因子β1 SMAD3 SMAD7 

分 类 号：R96[医药卫生—药理学]