曲尼司特对环孢素A慢性肾毒性大鼠肾间质骨桥蛋白表达及巨噬细胞浸润的影响  

Influence of tranilast on expression of OPN and interstitial ED1+ macrophages infiltration in rats with chronic cyclosporine A nephrotoxicity

作　　者：白亚君[1] 陶冶[1] 景宇[1] 付平[1] 吴欣[1] 李聃丹[1] 刘其峰[1] 

机构地区：[1]四川大学华西医院肾脏内科,四川成都610041

出　　处：《中国实用内科杂志：临床前沿版》2006年第10期1636-1639,共4页

摘　　要：目的观察曲尼司特对环孢素A(CsA)慢性肾毒性大鼠肾功能及肾脏病理的影响。方法选取四川大学华西医院于2005年9月至2006年2月给低盐饮食SD大鼠灌胃20mg/(kg.d)剂量的CsA,制作大鼠CsA慢性肾毒性模型,同时喂饲400mg/(kg.d)剂量的曲尼司特。于治疗第1、2、4周末观察肾脏病理变化,并测定骨桥蛋白(OPN)、单核巨噬细胞抗原(ED1)的表达。结果曲尼司特能明显改善慢性CsA肾毒性大鼠的体重下降,减少肾小管上皮细胞空泡变性和细胞坏死及间质炎细胞浸润和间质纤维化,对肌酐清除率(Ccr)下降无明显影响;免疫组化结果显示曲尼司特治疗组大鼠肾小管-间质ED1阳性巨噬细胞数量及OPN表达较模型组显著减少(P<0.05)。结论曲尼司特能减轻CsA慢性肾毒性的肾脏病理损伤,这一防治作用与其减少ED1阳性巨噬细胞浸润及下调OPN表达有关。Objective To evaluate the effect of tranilast on chronic cyclosporin A （CsA） nephrotoxicity rats and the possible mechanisms of protective effect of it. Methods Rats were on low salt diet and CsA was administered by gastric garage at a dose of 20mg/ （kg·d） for 28 days, and tranilast was gave to these rats in a dose of 400mg/ （kg·d）. The renal function and renal morphology were observed atl, 2 and 4 weeks after administration of tranilast. Results CsA induced the corruption of normal condition and weight lost were markedly delayed after administration of tranilast. On histopathology tranilast attenuated tubular cells vacuolations as well as interstitial damage including interstitial ED1 ＋ macrophages infiltration and focal interstitial fibrosis. Meanwhile, tranilast down - regulated the protein of OPN in kidney. Conclusion Tranilast can attenuate the structural changes of kidney in chronic CsA nephrotoxicity rats. Decreased CsA- related ED1 ＋ macrophages, OPN up -regulation expression in the kidney may be related to mechanisms of protective effect of tranilast in the treatment of CsA induced chronic nephrotoxicity.

关 键 词：曲尼司特 环孢素A 肾毒性 

分 类 号：R5[医药卫生—内科学]