心胸腺联合移植诱导大鼠同种异体移植免疫耐受

Immune tolerance induced by combined heart-thymus transplantation for heart allograft in rats

目的:研究心胸腺联合移植对大鼠同种异体移植心脏的抗排斥作用。方法:应用显微外科技术行心胸腺联合移植,通过移植心存活时间、病理学检查、CD4+,CD8+T细胞的浸润及检测血中和移植心中IL-2和IL-4水平,观察移植胸腺的作用。结果:对照组移植心平均存活(6.0±0.76)d,保留胸腺的大鼠行心胸腺联合移植其移植心平均存活(6.88±0.64)d(P<0.05);胸腺切除后行心胸腺联合移植可明显延长移植心的存活达(14.13±5.82)d(P<0.01),短期应用环孢素则可使移植心长期存活;在移植心获长期存活组其移植心及胸腺的病理改变及CD4+,CD8+T细胞的浸润均很轻微,且其血清及移植心组织中的IL-2降至较低水平,而IL-4则维持在较高水平。结论:无论保留或切除受体胸腺,心胸腺联合移植均有利于移植心的存活,而且胸腺切除后心胸腺联合移植对移植心有更显著的保护作用,短期应用免疫抑制剂则可诱导大鼠对同种异体移植心脏的耐受。

Objective allograft in rats. Methods To explore the role of combined heart-thymus transplantation for heart Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, infiltration of CD4^＋ , CD8^＋ T cells, level and mRNA expressions of IL-2 and IL-4 in the serum and cardiac grafts were investigated. Results Heart allograft in the controls had a survival time of （ 6.0± 0.76 ） d. Heart-thymus combined transplantation in non-thymectomized rats had a survival time of （ 6. 88 ± 0.64 ） d （ P 〈 0.05 ）. Heart-thymus combined transplantation in thymectomized rats led to an evident survival time of （14.13 ±5.82） d （ P 〈 0.01 ） for cardiac graft, which further obtained long term survival after short course of treatment with cyclosporine. Pathologic lesion and infiltration of CD4^＋ and CD8^＋ T cells in cardiac grafts showed mitigated in the long term survival group. IL-2 level in the serum and cardiac grafts maintained low level in the long term survival group, whereas IL-4 maintained high level. Conclusion Whether thymectomized or not in recipient rats, heart-thymus combined trans- plantation has a positive effect to protect cardiac graft. Furthermore, in thymectomized rats heart-thymus combined transpalantation may lead to evident survival prolongation of the heart grafts, which induces immune tolerance in short course of treatment with cyclosporine.