供体血管内皮细胞胸腺修饰对猪—猴心脏移植的影响

The Effect of Intrathymic Inoculation with Donor Endothelial Cells on Porcine to Monkey Heart Xenotransplantation

目的 探讨胸腺修饰对大动物异种心脏移植的影响 ,建立猪—猴异种心脏移植模型。方法 受体猕猴随机分成 4组 :对照组、照射组、照射 +胸注 16 4 0组和照射 +胸注供体血管内皮细胞 (VECs)组 ,对受体进行不同预处理后 ,作猪—猴腹腔异位心脏移植。同时在移植前作供体VECs溶解率和供体VECs与受体淋巴细胞 (猴T细胞 )的混合细胞反应检测。结果 照射 +胸注猪VECs组平均供心存活时间 (MeanSurvivalTime,MST)显著延长(12 4 .2± 4 .2h) ,超过照射组 (6 5 .2± 6 .6h)、照射 +胸注 16 4 0组 (6 3.0± 4 .0h)和对照组 (36 .2± 5 .9h) (P <0 .0 5 )。同时 ,该组供体VECs溶解率显著下降 (P <0 .0 5 ) ,受体T细胞增殖显著受抑制 (P <0 .0 5 )。结论 供体VECs(猪VECs)胸腺修饰可通过抑制受体 (猴 )T细胞的识别与增殖 ,减轻供心VECs激活 ,最终缓解延迟性异种排斥反应(DelayedXenograftRejection ,DXR) ,从而使供心存活时间显著延长 ,但不能完全克服DXR。

Objective To investigate the effect of intrathymic inoculation with donor VECs on heart xenotransplantation. Methods Donor(meishan pig) and recipient (rhesus monkey) were devided randomly into four groups: Control group (Group A), WBI(whole body irradiation) group(Group B) ,WBI plus intrathymic inoculation with 1640 group (Group C) and WBI plus intrathymic inoculation with donor VECs group(Group D). After different pretreatments to the recipients, the heterotopic heart transplantation from pig to monkey was performed. The grafted heart mean survival time (MST),the percentage of pig-VECs-lysed and the results of MCR (mixed cell reaction) (Pig VECs stimulate monkey T cells) before transplantation were observed. Results ①MST: Group D (124.2±4.2h)>Group B (65.2±6.6h)、Group C (63.0±4.0h)>Group A (36.2±5.9h),the MST of Group D was prolonged significantly ( P <0.05).②The percentage of the pig-VECs-lysed with monkey serums: Group D was apparently lower than the others ( P <0.05). ③The results of MCR: The proliferation of the recipient T cells in Group D was particularly inhibited compared with Group A、Group B and Group C ( P <0.05). Conclusion Intrathymic inoculation with donor VECs can delay DXR process and can prolong survival time of the grafted heart, but can't overcome DXR completely.