FTY720与ICAM-1单抗对小鼠-大鼠异种心脏移植抗排斥的作用  

Effect of mono and combination therapy with FTY720 and ICAM-1 mAb for mouse-to-rat cardiac xenotransplantation

作　　者：熊海波[1] 黄祖发[1] 叶启发[1] 夏穗生[2] 

机构地区：[1]中南大学湘雅三医院器官移植研究院,长沙410013 [2]华中科技大学同济医学院器官移植研究所,武汉430030

出　　处：《中南大学学报（医学版）》2007年第1期41-46,共6页Journal of Central South University ：Medical Science

摘　　要：目的:研究FTY720与ICAM-1单抗(mAb)对小鼠-大鼠异种心脏移植的抗排斥作用。方法:采用小鼠-大鼠腹部心脏移植,观察移植心存活时间、病理检查、CD4和CD8细胞的浸润程度及检测血中IL-2,IFN-γ,IL-4以及IgM抗体水平。结果:对照组移植心平均存活时间为(2.75±0.43)d。单用ICAM-1mAb组移植心存活时间无明显延长,单用FTY720大剂量组移植心平均存活(4.25±0.71)d(P<0.01);FTY720与ICAM-1mAb大剂量联合用药组移植心存活时间平均(10.25±2.12)d(P<0.01)。联合用药组的病理反应、T细胞浸润及IL-2,IFN-γ,IgM水平明显减轻或降低;IgM水平与移植物存活时间呈负相关(R=-0.754,P<0.01)。结论:FTY720与ICAM-1mAb单一用药对异种移植的抗排斥作用不明显,联合用药可有效延长异种心脏移植的存活时间并能抑制异种抗体的产生。Objective To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation. Methods Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4^＋ , and CD8^＋ T cells and levels of serum IL-2 Results Survival time of xenografts was （ 2.7 5 ± 0.4 , IFN-γ, IL-4, and IgM were investigated. 3 ） d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of （4.25 ± 0.71 ）d （P 〈 0.01 ）. Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with （ 10.25 ±2. 12 ） d （ P 〈 0.01 ）. Levels of serum IL-2, IFN-γ and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time（ R = - 0. 754, P 〈 0. 01 ）. Conclusion The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies.

关 键 词：FTY720 ICAM-1 mAb 异种移植 急性血管性排斥反应 小鼠 大鼠 

分 类 号：R654.2[医药卫生—外科学]