胸腺修饰联合照射预处理受体在猪-猴心脏移植中对补体的影响及机理探讨  

Study on the effect of the complement in the discordant heart xenotransplantation produced by intrathymic inoculation with xenogeneic antigen and whole-body γ-radiation using the model of pig to monkey

作　　者：瞿冀琛[1] 沈振亚[2] 姜格宁[3] 丁嘉安[3] 高文[3] 倪斌[1] 张治[1] 何建明[1] 余云生[1] 叶文学[1] 

机构地区：[1]苏州大学附属第一医院,苏州215006 [2]苏州大学附属第一医院心胸外科和器官移植研究室,苏州215006 [3]同济大学附属上海市肺科医院胸外科,上海200433

出　　处：《中国免疫学杂志》2008年第3期231-235,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(批准号:39770731)

摘　　要：目的:探讨补体在异种大动物猪-猴心脏移植排斥反应中的作用。方法:选用猪-新生猴腹腔心脏异位模型,通过异种胸腺修饰加60Coγ照射途径。结果:预处理组移植前补体水平较空白组无明显变化,但随着IgM、IgG水平的上升,排斥时C3、CD46水平显著降低。在照射+胸腺注射组中,猕猴特异性抗猪抗体IgM及IgG的上升速度均较照射组和空白组明显延缓,且存活期较空白组明显延长。MLR检测在照射+胸腺注射组接受脾细胞胸腺内注射后第3周,其刺激效应较空白组、照射组下降明显(P<0.01)。结论:补体通过经典途径参与超急性及延迟性异种排异反应的发生,补体本身并不直接损伤内皮细胞,而需要有抗体的参与。通过异种胸腺注射联合照射预处理在抑制T细胞免疫及体液免疫方面有重要作用,但尚无法起到抑制异种排异反应中补体激活的作用。Objective： To investigate the validation of the complement in the discordant heart xenotransplantation produced by intrathymic inoculation with xenogeneic antigen and whole-bedy γ-radiation using the model of pig to monkey. Methods： In this experiment, pig and monkey were selected as donor and recipient respectively. And were divided randomly into three groups. The blank group（group A）：recipients didn＇t accept any treaunents but heart xenotransplantation; Whole body irradiation group（group B） ： received 3 Gy（^60Co）WBI on 28 day before transplantation; Irradiation and intrathymic injection group（group C ） ： the monkeys pretreated by WBI and the intrathymic injection of pig spleen cells. In erery group, monkeys were performed heterotopic heart xenotransplantation in order to observe the survival time of cardiac xenografts. Results： The experimental results of this study showed that the survival time of donor heart in the irradiation and intrathymic injection （IT and WBI） group （ 91.1±22.8 ） was significantly longer than the blank group （36.6 ±5.8 ） （ P 〈 0.01）. The results of MLR showed that there was significant reduction in the IT and WBI group than in the blank group.After xenotransplantation, the level of elicited xenorecative antibody（EXA） IgM and IgG in the group C ascended slower than that in group A and group B obviously（ P 〈 0.01 ）.After rejection the level of CD46 declined greaterly than that before transplantation. Conclusion： These results suggest that pretreatment with IT and WBI could induce T cells immune suppression, and restrain the production of elicited xenorecative antibody IgM and IgG. But it could not restrain the activation of complement via the classical pathway in the hyperacute rejection and delayed xenograft rejection.

关 键 词：异种心脏移植 胸腺修饰 免疫抑制 补体 

分 类 号：R392.4[医药卫生—免疫学]