大剂量免疫抑制剂预处理后骨髓移植诱导小鼠皮肤移植耐受的实验研究  

Donor specific tolerance for MHC mis-matched murine skin allograft induced by donor bone marrow transplantation with precondition of high dose immunosuppressants

作　　者：马朝来[1] 张同琳[1] 雷玉涛[1] 罗刚[1] 王坤[1] 孙和新[1] 

机构地区：[1]北京大学第三医院普通外科,100083

出　　处：《中华器官移植杂志》2004年第6期360-363,共4页Chinese Journal of Organ Transplantation

基　　金：北京大学器官移植中心985项目基金资助

摘　　要：目的　用大剂量免疫抑制剂作为骨髓移植前受者的预处理 ,诱导其对供者特异性器官移植免疫耐受 ,并探讨宏嵌合的形成与移植耐受的关系。方法　雄性C5 7BL/ 6和雌性BALB/c小鼠作为皮肤移植的供者和受者。实验分为 1 1组 :第 1组为对照组 ,仅作皮肤移植 ,不做其他处理 ;第 2组为单纯供者骨髓细胞移植 (BMT)后进行皮肤移植 ;第 3～ 5组 :分别使用免疫抑制剂他克莫司(FK5 0 6 )、环孢素A(CsA)、环磷酰胺 (CTX)后进行皮肤移植 ;第 6～ 8组 :分别应用FK5 0 6、CsA、CTX预处理后作骨髓移植 ,再进行皮肤移植。前 8组皮肤及骨髓供者均为雄性C5 7BL/ 6小鼠。第 9～ 1 1组 :处理同第 6～ 8组 ,但移植皮肤来自无关供者雄性ICR小鼠 ,以验证耐受的特异性。每组受鼠 6只。观察皮肤移植存活时间、皮肤的排斥反应 ,并用多聚酶链式反应 (PCR)检测嵌合体的形成。结果　单独应用常规剂量的供者骨髓细胞输注或短期的免疫抑制治疗并不能延长移植物的存活 ,也没有宏嵌合形成。而 6～ 8组的皮肤移植物存活时间较各对照组明显延长 ;宏嵌合检查呈阳性。来自无关供者的皮片存活时间无延长。结论　采用短期应用大剂量免疫抑制剂这一温和的非照射预处理方法 ,再输注供者骨髓细胞 ,可获得一定程度的免疫耐受 ,达到延长皮肤移植物存活的?Objective To establish a non-irradiated precondition strategy for successful donor specific transplantation tolerance induced by bone marrow transplantation which may be introduced to clinical application by a murine model.Methods Male C57BL/6 and female BALB/c mice were used as skin transplant donors and recipients respectively. In all, 11 groups were studied: group 1, control mice with skin graft and without any other treatment; group 2, mice receiving only donor bone marrow transplantation (DBMT) before skin transplantation; groups 3～5, mice administrated by only high dose FK506, CsA or CTX respectively and then skin transplantation; groups 6～8, mice receiving DBMT preconditioned by high dose FK506, CsA or CTX respectively and followed by skin transplantation. Both skin and bone marrow donors were male C57BL/6 mice in above 8 groups. Mice in groups 9～11 were treated almost equally to groups 6～8 except that skin grafts were from the third party ICR donors to prove specificity of tolerance. Every group included 6 recipients. Survival time of skin graft was recorded. Macrochimerism were examined by PCR method.Results Neither standard dose DBMT nor high dose immnodepressants alone could prolong skin graft survival, and macrochimerism was not detected, either. But skin graft survival time was significantly prolonged and macrochimerism was also detected in mice of 6～8 groups. Survival time of skin graft from the third party mice was not prolonged. Conclusions Bone marrow transplantation preconditioned with high dose immunosuppressants and without irradiation can induce donor specific transplantation tolerance and prolong murine skin graft survival. It may work through the mechanism of establishment of macrochimerism.

关 键 词：皮肤移植 供者 免疫抑制剂 耐受 大剂量 骨髓移植 输注 雄性 嵌合 雌性 

分 类 号：R617[医药卫生—外科学]