免疫抑制剂联合供体骨髓输注诱导肝移植受体长期存活的研究  

Posttransplant Administration of Allogeneic Bone marrow Transfusion Combined with Immunosuppressive Agents Induces Rat Hepatic Allograft Tolerance

作　　者：祝哲诚[1] 钟福全[1] 李剑锋[1] 刘文文[1] 裘正军[1] 彭志海[1] 

机构地区：[1]上海交通大学第一人民医院普外科上海市器官移植临床医学研究中心,上海200080

出　　处：《上海交通大学学报（医学版）》2006年第6期591-594,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委科技发展基金(014119033)资助项目

摘　　要：目的研究他莫克司(FK506)、霉酚酸酯(MMF)、抗CD28单克隆抗体(anti-CD28mAb)为主要免疫抑制方案联合供体骨髓输注,对大鼠肝移植受体存活时间的影响。方法建立大鼠原位肝移植模型:①A组(n=6):同品系移植,供、受体同为W istar大鼠或SD大鼠;②B组(n=14):W istar大鼠为供体,SD大鼠为受体(W istar→SD),术后不采取任何治疗措施;③C组(n=7):W istar→SD,术后FK506、MMF联合应用2 d;④D组(n=6):W istar→SD,术后FK506、MMF联合应用2 d,然后单独应用FK506共4 d;⑤E组(n=6):W istar→SD,术后供体骨髓输注,其余处理同D组;⑥F组(n=3):W istar→SD,术后供体骨髓输注,术后第1天应用1次anti-CD28mAb,FK506、MMF术后联合应用2 d,然后单独应用FK506共2 d。观察各组移植物的存活和排斥发生情况及其组织病理学改变。结果A组大鼠均存活100 d以上;B组大鼠死于急性排斥反应,中位存活时间为15.5 d;C、D组大鼠中位存活时间分别为46 d和68 d;E、F组大鼠均存活100 d以上,组织病理学检查门静脉周围和肝组织内未见明显炎症细胞浸润。结论W istar大鼠与SD大鼠间肝移植,属于高免疫排斥型动物组合,可作为大鼠肝移植免疫排斥和免疫耐受研究的有效品系组合;移植同时供者骨髓细胞的输注可获得移植肝的长期存活;anti-CD28mAb和短时间FK605、MMF联合应用具有协同作用。Objective To observe the liver allografts survival time and rejection episodes after administration of immunosuppressive agents consisted of FK506, MMF and anti-CD28mAb combined with or without administration of allogeneic bone marrow transfusion on the time of operation. Methods Orthotopic rat liver transplantation was performed in a Wistar-to-SD strain combination. All the transplantation models were divided into six groups： Group A （ n = 6） , Wistar-to-Wistar or SD-to-SD ; group B （ n = 14） , Wistar-to-SD without immunosuppression ; group C （ n = 7） , Wistar-to-SD, FK506 ＋ MMF for two days; group D （n = 6） , Wistar-to-SD, FK506 ＋ MMF for two days and then FK506 alone for four days; group E （n =6） , Wistar-to-SD, FK506 ＋ MMF for two days and then FK506 alone for four days with allogeneic bone marrow transfusion on the time of operation; group F （n = 3） , FK506 ＋ MMF for two days and then FK506 alone for two days with allogeneic bone marrow transfusion on the time of operation, and administration of anti-CD28mAb in the first day after operation. The survival time, rejection episodes and pathological changes were observed. Results Recipients of syngeneic control grafts （group A） survived for more than 100 d. Untreated SD recipients of Wistar liver allografts （group B） died of acute rejection at a median of 15.5 d. The median survival time of group C and group D were 46 d and 68 d, respectively. Group E and group F survived for more than 100 d with no significant portal or lobular cellular infiltration microscopically. Conclusion The combination of donor liver of Wistar rats and recipient SD rats is a high responder model and can be effectively used to study allograft rejection and liver transplantation tolerance. Treatment of the recipients with donor bone marrow at the completion of transplantation can lead to long-term acceptance of the transplanted liver. The synergistic action of short-time administration of FK506,MMF plus anti-CD28mAb could be demonstrated.

关 键 词：肝移植 移植物排斥 免疫耐受 供者特异性输注 

分 类 号：R657.3[医药卫生—外科学] R392.4[医药卫生—临床医学]