他克莫司通过抑制GITRL减轻大鼠肝移植排斥反应的研究  

Tacrolimus alleviates acute liver graft rejection by inhibiting glucocorticoid-induced tumor necrosis factor-related protein ligand in rats

作　　者：魏思东[1] 龚建平[1] 李金政[1] 黄中荣[2] 

机构地区：[1]重庆医科大学附属第二院肝胆外科/重庆市肝胆外科重点实验室,重庆400010 [2]重庆医科大学附属永川医院,重庆402160

出　　处：《南方医科大学学报》2011年第9期1480-1483,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30772098;81070374;30801126);重庆市卫生局资助项目(2010-2-260)~~

摘　　要：目的探讨他克莫司(FK506)抑制大鼠肝移植排除反应中的作用机制。方法建立大鼠原位肝移植模型,分为3组。耐受组为Brown Norway(BN)到Lewis肝移植;排斥组为Lewis到BN肝移植;他克莫司(FK506)组在建立排斥模型基础上于术后注射FK506。术后7 d检测肝组织病理改变及糖皮质激素诱导的肿瘤坏死因子相关蛋白配体(GITRL)的表达、Kupffer细胞GITRL的表达及细胞因子的改变。结果与耐受组比较,排斥组肝脏及kupffer细胞中GITRL表达升高,采用FK506后,降低了GITRL表达(P<0.05)。与耐受组比较,排斥组血清及kupffer细胞中IFN-γ表达升高,IL-10降低(P<0.05),而在FK506组,与排斥组比较,血清及kupffer细胞中IFN-γ表达降低,IL-10表达升高(P<0.05)。结论 FK506能减轻大鼠肝移植后的急性排斥反应,其机制与降低GITRL的表达有关。Objective To investigate the mechanism underlying the inhibitory effect of tacrolimus（FK506） against acute liver graft rejection.Methods Rat models of orthotopic liver transplantation were divided into 3 groups,namely the tolerance group with Brown Norway（BN） rats as the donors and Lewis rats as the recipients,rejection group with Lewis rats as donors and BN rats as recipients,and FK506 group with the same donor-recipient pair as in the rejection group and FK506 treatment.The recipients were sacrificed 7 days after the transplantation,and the hepatic histology,cytokine levels,and glucocorticoid-induced tumor necrosis factor-related protein ligand（GITRL） expression in the liver and Kupffer cells were observed and detected.Results Compared with the tolerance group,the rejection group showed increased GITRL expressions in the liver and Kupffer cells（P〈0.05）,which was significantly lowered by FK506 treatment（P〈0.05）.Acute liver graft rejection caused significantly elevated interferon-γ（IFN-γ） levels and decreased interleukin-10（IL-10） levels in the plasma and Kupffer cells（P〈0.05）,and these changes were obviously attenuated by FK506 treatment（P〈0.05）.Conclusion The effect of FK506 in suppressing acute liver graft rejection is probably associated with down-regulated GITRL expression in the liver and Kupffer cells.

关 键 词：GITRL 肝移植 急性排斥反应 KUPFFER细胞 他克莫司 

分 类 号：R657.3[医药卫生—外科学] R392.4[医药卫生—临床医学]