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《中国微创外科杂志》[ISSN:1009-6604/CN:11-4526/R]

卷:

04

期数:

2004年5期

页码:

438-440

栏目:

基础研究

出版日期:

2004-05-30

文章信息/Info

Title:

Tolerance for murine skin allograft induced by bone marrow transplantation with the precondition of Tacrolimus (FK506): An experimental study

作者:

马朝来　 张同琳　 王坤　 孙和新　

北京大学第三医院普通外科,北京,100083

Author(s):

Ma Zhaolai;  ZhangTonglin;  WangKun;  et al.

Department ofGeneral Surgery, Peking University ThirdHospital, Beijing100083, China

关键词:

皮肤移植;  免疫耐受;  宏嵌合;  小鼠;  骨髓移植;  FK506

Keywords:

Skin transplantation; 　Immunological tolerance; 　Macrochimerism; 　Mouse; 　Bone marrowtransplantation; 　FK506

分类号:

R-332

文献标志码:

A

摘要:

目的探讨短期大剂量FK506作为宏嵌合诱导供体特异性耐受中,骨髓移植前对受体预处理方法的可行性及临床实用性. 方法 100只雄性C57BL/6和60只雌性BALB/C小鼠分别作为皮肤移植的供体和受体,雄性ICR小鼠15只作为无关第三品系用以检测移植耐受状态的特异性.将60只受体小鼠随机分为5组,即无处理对照组、单纯FK506组、单纯骨髓细胞移植(BMT)组、实验组(FK506+BMT)和无关供体对照组,每组12只.FK506诱导及维持方案是皮肤移植前对受体小鼠先给予大剂量FK506腹腔注射(3 mg/kg×2 d),移植当天尾静脉输注2×107个骨髓细胞,再以小剂量FK506(0.5 mg/kg×7 d)短期维持治疗.观察皮肤移植存活时间、对第三方皮肤的排斥反应及对供体鼠的单向混合淋巴细胞反应,并用多聚酶链式反应(PCR)检测嵌合体的形成. 结果常规剂量的骨髓输注或短期FK506治疗并不能延长移植物的存活时间,也没有宏嵌合形成.实验组皮肤移植物存活时间(24.0±1.5)d比无处理对照组(9.6±1.1)d、单纯FK506组(10.5±1.6)d、单纯骨髓细胞移植组(10.3±1.5)d、无关供体对照组(9.8±1.1)d明显延长(P<0.05).混合淋巴细胞反应实验组供者特异性抑制率80.55%±14.10%明显高于单纯FK506组38.65%±12.43%及单纯骨髓细胞移植组35.41%±8.99%(P<0.05),实验组宏嵌合呈阳性. 结论采用短期大剂量FK506这一温和的非照射预处理方法,可获得一定程度的免疫耐受,延长移植物存活.移植前输注供体骨髓细胞能够促进宏嵌合的形成及移植物的存活.

Abstract:

Objective　To investigate the feasibility and practicability of the precondition using high-dose of Tacrolimus (FK506) before the bone marrow transplantation (BMT) for macrochimerism specific tolerance.　Methods　One hundred male C57BL/6 mice and 60 female BALB/C mice were respectively used as donors and recipients of skin transplantation, and another 15 male ICR mice were used as the third germ line to detect the specificity of tolerance. Sixty recipient mice were divided randomly into 5 groups: blank control group, FK506 group, BMTgroup, experimental group (FK506+BMT) and third party donor control group, with 12 mice in each group. Before the skin transplantation, high-dose abdominal injection of FK506 (3 mg/kg×2 d) was performed in recipient mice. On the transplantation day a bonus of 2×107bone marrow cells were injected through the tail vein. Then a short period of low-dose FK506 (0.5 mg/kg×7 d) was administrated for maintenance treatment. The survival time of skin grafts, reject reaction against the third party skin, and mixed lymphocyte culture (MLC) were observed. The polymerase chain reaction (PCR) was employed for the detection of macrochimerism.　Results　Routine dose of bone marrow cells infusion or short period of FK506 administration led to neither prolonged survival time of grafts nor the formation of macrochimerism. The skin graft survival time was significantly prolonged in the experimental group (24·0±1·5 d), as compared with the blank control group (9·6±1·1 d), the FK506 group (10·5±1·6 d), the BMT group (10·3±1·5 d), and the third party donor control group (9·8±1·1 d), respectively (P<0·05). MLC demonstrated that the donor specific inhibition of lymphocyte proliferation in the experimental group (80·55%±14·10%) was significantly higher than that in the FK506 group (38·65%±12·43%) and the BMT group (35·41%±8·99%), respectively (P<0·05). Macrochimerism developed in the experimental group.　Conclusions　A non-irradiated precondition method, high-dose FK506 administration for a short period may induce certain extent of immunological tolerance and prolong the survival time of murine skin grafts. Donor bone marrow cells infusion before the transplantation may promote the formation of macrochimerism and the survival of grafts.

备注/Memo

备注/Memo:

基金项目：北京大学器官移植中心"985"与移植相关的基础与临床相结合课题项目基金资助(批准号:985B4)

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更新日期/Last Update: 2014-06-09