来氟米特和环孢素A对异种心脏移植排斥反应中核因子κB信号传导的抑制作用  

Inhibitory effects of leflanomide and cyclosporine on NF-κB signal pathway in mouse to rat cardiac xenograft

作　　者：杨光伦[1] 姚榛祥[1] 黄平[1] 涂刚[1] 

机构地区：[1]重庆医科大学附属第一医院普外科,400016

出　　处：《中华器官移植杂志》2008年第9期517-521,共5页Chinese Journal of Organ Transplantation

摘　　要：目的探讨联合应用来氟米特（Lef）和环孢素A（CsA）对大鼠异种心脏移植排斥反应中核因子κB（NF-κB）信号传导通路中核因子κB抑制因子激酶α／β（IKKα／β）、NF-κB P65、核因子κB抑制因子α（IκBα）、细胞间粘附分子-1（ICAM-1）表达以及NF-κB DNA结合活性的影响。方法以NIH小鼠为供者，Wistar大鼠为受者，施行颈部心脏移植，CsA组受者术后接受CsA腹腔注射，Lef组受者术后接受Lef灌胃，联合用药组受者术后接受CsA和Lef治疗，另设术后不接受任何药物处理的空白对照组。术后观察移植心脏存活时间，发生排斥反应时，切取移植心脏，进行组织病理学观察，采用免疫组织化学和Western印迹法检测各组移植心肌组织中IKKα／β、NF-κB P65、IκBα和ICAM-1的表达，凝胶电泳迁移率法检测NF-κB DNA结合活性。结果空白对照组、CsA组、Lef组及联合用药组移植心脏的存活时间分别为（2．17±0．41）d、（2．50±1．05）d、（4．17±1．33）d和（6．50±2．56）d，联合用药组明显长于其它3组（P〈0．05），Lef组明显长于空白对照组（P〈0．05）。4个组心肌组织中IKKα／β、NF-κB P65、IκBα和ICAM-1的表达由强到弱依次为空白对照组、CsA组、Lef组、联合用药组，其电泳条带积分吸光度值显示，Lef组的IKKα／β、NF-κB P65、IκBα和ICAM-1的表达明显低于空白对照组和CsA组（P〈0．05），而联合用药组明显低于其它3组（P％0．05）。Lef组的NF-κB DNA结合活性明显低于空白对照组及CsA组，联合用药组的NF-κB DNA结合活性明显低于其它3组，差异均有统计学意义（P〈0．05）。结论联合应用Lef和CsA可显著延长大鼠移植的异种（小鼠）心脏的存活时间，这可能与NF-κB信号通路中的IKKα／β、NF-κB P65、IκBα、ICAM-1表达及NF-κB DNA结合活性受到抑制有关。Objective To investigated the effects of leflunomide （Lef） in combination with cyclosporine （CsA） on IKKα/β, NF-κB P65, IκBα, ICAM-1 and NF-κB DNA binding activity in NF-κB signal pathway in mouse to rat cardiac xenografts. Methods NIH mice and Wistar rats served as donors and recipients respectively. Mouse to rat heterotopic heart transplantation was performed （in the neck）. The experiments were divided into 4 groups： CsA was injected intraperitoneally after operation in the CsA group; Lef was given in the Lef group by gastric tube after operation; CsA combined with Lef was administered after operation in CsA＋ Lef group; In the control group, the recipients didn＇t receive any medicine treatment. After operation, the survival of the transplanted heart was observed. The histophathologie examination was done in the transplanted heart. The expression of IKKα/β, NF-κB P65, IκBα and ICAM-1 and NF-κB DNA binding activity in cardiac xenograft tissues were determined by immunohistochemistry and Western blot as well as electrophoretic mobility shift assay （EMSA） in each group. Results The survival time of the cardiac xenografts in control group, CsA group, Lef group and CsA ＋ Lef group was （2. 17 ± 0. 41）, （2. 50 ± 1. 05）, （4. 17 ± 1.33） and （6. 50±2. 56） days, respectively, significantly longer in CsA ＋ Lef group than in other three groups （P〈0. 05）, and significantly longer in Lef group than in control group （P〈0. 05）. The expression of IKKα/β（IOD） in cardiac xenograft tissues in control group, CsA group, Lef group and CsA ＋ Lef group was （137.1 ±4.0）, （149.7±6.5）, （111.6± 14. 6） and （81.4± 15.9）, the expression of NF-κB P65 （IOD） was （261.3±31.6）, （263.1 ±28.8）, （173.5±5.9） and （67.8±3.8）, the expression of IκBα （IOD） was （88.6±6.7）, （80.4±3.5）, （64.8±8.9） and （37.3±4.4）, the expression of ICAM-1 （IOD） was （155. 4 ± 5. 3）, （ 150. 7 ± 5. 1）, （ 104. 7 ± 6.

关 键 词：移植 异种 心脏移植 免疫抑制剂 NF-κB 

分 类 号：R654.2[医药卫生—外科学]