近交系大鼠后肢移植模型的建立及意义

Establishment and evaluation of hind limb allotransplantation model in rats

目的:介绍异体复合组织移植研究中操作难度较大的大鼠后肢移植模型的建立方法,操作体会及此动物模型在复合组织移植中的意义。方法:以近交系BrownNorway(RT1n)大鼠为供体,Lewis(RT11)大鼠为受体,吻合股动、静脉为供血血管,进行近交系大鼠后肢异体移植。实验分为2组:急性排斥组(A组)术后不予免疫抑制治疗;免疫抑制组(B组)术后腹腔注射FK506剂量为1mg/kg/天。术后观察移植肢体的排斥情况及其存活时间,并取皮肤进行组织病理学检查,以此对动物模型的可靠性和实用性进行评价。结果:A组移植皮瓣均在术后(4±1)天发生明显的逐渐加重的急性免疫排斥反应;B组移植肢体均可良好存活,存活时间均>100天。皮肤组织病理学检查上,A组有血管炎、毛囊炎及真皮炎症等典型急性排斥反应表现;B组均无明显免疫排斥病理学表现。术后IL-2水平与肢体外观表现及病理学检查所见排斥反应程度相一致。结论:近交系大鼠后肢移植模型是得到广泛承认的复合组织移植模型,也是最具挑战性的动物模型之一,完善近交系大鼠后肢移植模型的建立方法,使模型不断规范化,对复合组织异体移植研究的发展具有重要意义。

Objective To demonstrate the establishment of the rat hind limb allotransplantation model which is one of the most challenging models for composite tissue allotransplantation. Methods In our study, Lewis rats were used as recipients and Brown Norway rats were used as donor. We harvest the hind limb allografts of Brown Norway rats based in the femoral artery and vein, then the allograts were orthotopicly transplanted to Lewis rats. 30 couples of rats were divided in 2 groups： Group A, acute rejection group, in which no immunosuppressor was given to the recipients after allotransplants. Group B, immunosuppression group, in which all recipients was injected with FK506 as lmg/kg/day just after allotransplants. Observe the survival days and rejection time of hind limb allografts, histopathological outcomes , and the level of IL-2 to evaluate the stability and reliability of this model. Results The rejection time was （4±1）d in Group A and （〉100）d in Group B, respectively, histopathological outcomes and the level of IL-2 were coincident with the rejection observed outside of the hind limb allografts. Conclusion Rat hind limb allotransplantation model is a stable, widely accepted and very important model for composite tissue allotransplantation.