同种异体肢体移植特异性免疫耐受诱导方案的研究  

Research of induction of donor-specific tolerance with sublevel dose irradiation

作　　者：石作为[1] 张信英[1] 

机构地区：[1]哈尔滨医科大学附属第一临床医院骨科,黑龙江哈尔滨150001

出　　处：《中国现代医学杂志》2008年第13期1837-1840,共4页China Journal of Modern Medicine

基　　金：黑龙江省教育厅资助项目(No:11531122)

摘　　要：目的探讨联合应用亚致死量放射线照射、氟达拉滨及骨髓腔内骨髓移植对诱导大鼠同种异体肢体移植产生特异性免疫耐受的影响。方法以纯系SD大鼠及Wistar大鼠为供受体,行同种异体右后肢移植。40只大鼠肢体移植后随机分为4组:A组:仅进行肢体移植;B组:在肢体移植前1d,受体给予亚致死量60Co照射及腹腔内注射氟达拉滨;C组:肢体移植当天受体接受供体骨髓腔内骨髓移植;D组:受体联合应用亚致死量照射、注射氟达拉滨及骨髓腔内骨髓移植,用法及用量同B、C组。观察移植物排斥反应征象及存活情况,并对D组产生免疫耐受大鼠进行SD大鼠及DA大鼠皮肤移植以及脾细胞中细胞因子mRNA检测。结果与其他实验组相比,D组移植物发生排斥反应的时间及存活时间均显著延长(P<0.01)(>120d);D组大鼠仅对第3方DA大鼠的皮肤呈现强烈的免疫反应;与A组大鼠相比,D组大鼠Th1型细胞因子的表达明显降低,而Th2型细胞因子的表达明显增高。结论联合方案可以诱导大鼠同种异体肢体移植产生特异性免疫耐受。[Objective] To study the effect on the immunologic reaction of limb allouansplantation by using method of intra-bone marrow injection of donor bone marrow cells combined with sublevel dose irradiation and Fludarabine. [Method] The inbred SD rats were chosen as donors and inbred Wistar rats as recipients. 40 recipients were divided into four groups randomly after limb alhransplantation. Rats in group A received transplantation only; group B rats received irradiation in the sublethal level and Fludarabine the day before transplantation. In group C, bone marrow cells were directly injected into the intra-bone marrow cave of recipients immediately after transplantation. In group D, using a combination of the injection of Fludarabine, irradiation and injection of donor bone marrow cell. The condition of survival and rejection of grafts was observed. Tolerance rats in group D were received SD and DA rat skin grafting and analysis of cytokine mRNA expression. [Results] Compared with other groups, mean survival time of limb allografts was prolonged obviously in group D （P 〈0.01）（〉120 d）. Rats in group D had a low reaction to the transplanted SD skins, but had strong reactions to DA rat＇s skin. The levels of IL-2 and IFN-7 mRNA expression in tolerant rats in group D were much lower than those in the control rats. The levels of IL- 4 and IL-10 mRNA in tolerant rats in group D were much higher than those in the control rats. [ Conclusion] Combination method can induce donor-specific tolerance in limb alltransplantation in rats.

关 键 词：移植 免疫耐受 放射疗法 骨髓细胞 大鼠 

分 类 号：R-332[医药卫生]