【摘要】 目的比较多种不同的预处理方案,筛选一种具有低毒性、能诱导出长期稳定的同种异基因移植免疫耐受的非清髓性预处理方案。方法受体BALB/C(H-2d)小白鼠,供体C57BL/6(H-2b)黑小鼠,建立小鼠耳后心脏移植模型。在心脏移植(HT)前,给予受体腹膜腔内注射抗胸腺细胞血清(ATS)5次、亚致死剂量全身X线照射(TBI)1次、骨髓移植(BMT)等7个不同组合的预处理方案,术后观察移植心脏跳动情况,于骨髓移植后第28 d检测外周血中嵌合体。结果一实验组(ATS+TBI450 cGy+BMT+HT)采用受体在心脏移植前接受5次腹膜腔内注射ATS、1次TBI(450 cGy)、静注供者骨髓细胞5×107个等处理的非清髓性治疗方案,移植心脏(9/10)存活>100 d;骨髓移植术后第28 d检测外周血,均出现完全异体细胞嵌合状态。结论早期应用ATS与亚致死量TBI有着协同作用;非清髓性预处理方案(ATS+亚致死量TBI(450 cGy)+BMT)既获得了持久、稳定的供者造血干细胞嵌合体,也诱导出同种异基因移植长期特异性免疫耐受。更多还原

【Abstract】 Objective As a pre-clinical experimental research,we selected a superior perioperative conditioning regimen,which should be low-toxic,sutable for clinical practice tolerance with comparing variety of host-conditioning regimens.Methods The recipients,BALB/C mice(H-2d),were conditioned with variety of combination of TBI,ATS and infusion of bone marrow cells(5×107) from donor C57BL/6 mice(H-2b) and were divided into 7 groups,and then neonatal donor heart allografts were transplanted into the pinna of the ear of recipients without any other immunosuppressive therapies.Heart grafts were monitored daily for visible contractions under microscope(magnification×10),and survival was based on the time interval until contractions stopped.Chimera in peripheral blood of hosts were routinely analyzed by flow cytometry on day 28 after BMT.Results Comparison of heart graft survival time(days) among groups: 9 of 10 heart grafts in hosts conditionated with combination of ATS+sublethal TBI(450 cGy)+BMT survived for more than 100 days,and 1 of 10 heart grafts in the group survived for 69 days.Heart graft survival time was non-significantly different between ATS+TBI(450 cGy)+BMT group and lethal TBI(800 cGy)+BMT group(P>0.05).Heart graft survival time in hosts treated by TBI(450 cGy)+BMT was(22.1±9.4) days averagely,which was significantly different from that in the previous two groups(P<0.001).Hosts administered by ATS,ATS+TBI(450 cGy),TBI(450 cGy) or ATS+BMT rejected their allogeneic heart grafts within 45 days after heart transplantation.All of hosts conditioned with TBI(450 or 800 cGy)+BMT and ATS+TBI(450 cGy)+BMT got complete donor-cell chimera in blood on day 28 after BMT.Conclusion Pre-transplant of ATS+sublethal TBI+BMT was the most effective among variety of non-myeloablative host-conditioning regimens using different conditions of TBI,ATS and BMT.It can induce long-term,stable donor-specific immune tolerance in mice.The reasonable schedule of treatment makes it more potential applicability in allogeneic grafts.更多还原