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目的 探讨脾脏在仓鼠到大鼠异种肝移植中的体液免疫、细胞免疫作用。方法 三袖套法建立仓鼠到大鼠原位肝移植模型 ,观察移植术后肝脏和脾脏的病理变化 ;采用补体介导的细胞毒实验检测异种肝移植术后血浆中抗仓鼠抗体滴度的变化 ;运用免疫组织化学的方法检测脾脏中大鼠抗体的产生、脾脏增殖细胞核抗原 (PCNA)的表达 ;并观察环孢素A、环磷酰胺、切脾对移植术后生存时间及免疫排斥反应的影响。结果 异种肝移植术后免疫排斥反应发生时 ,脾脏急剧增大 ,边缘区明显增厚 ,产生大量抗体 ,血浆中抗体滴度显著增高 ,移植物遭受破坏。环磷酰胺可选择性抑制脾脏边缘区的增殖 ,明显降低血浆抗体滴度 ;切脾 +环孢素A可抑制其免疫排斥反应 ,生存时间显著延长 (P <0 .0 1) ,但延迟 3d切脾则不能延长其生存时间 (P >0 .0 5 )。结论 在异种肝移植免疫排斥反应中 ,介导体液免疫的抗体主要来源于脾脏边缘区的免疫细胞 ,术后 3d即已到达免疫反应场所 ,在其细胞免疫中发挥重要作用。
Objective To investigate the humoral and cellular immunity of spleen in hamster-to-rat xenotransplantation. Methods The three-cuff method was used to establish the orthotopic liver transplantation model in rats. The pathological changes of the liver and spleen were observed after transplantation. The complement-mediated cytotoxicity assay was used to detect the change of anti-hamster antibody titers Immunohistochemistry was used to detect the production of rat antibodies in the spleen and the expression of proliferating cell nuclear antigen (PCNA) in spleen. The effects of cyclosporine A, cyclophosphamide and splenectomy on the survival time and immune rejection after transplantation were observed influences. Results When the immune rejection occurred after xenotransplantation, the spleen increased sharply and the marginal zone was obviously thickened, producing a large number of antibodies. The antibody titers in plasma were significantly increased and the graft was damaged. Cyclophosphamide can selectively inhibit the proliferation of the marginal division of the spleen and significantly reduce the antibody titer in plasma. Splenectomy plus cyclosporin A can inhibit the immune rejection and prolong the survival time significantly (P <0.01) Splenectomy can not extend its survival time (P> 0.05). Conclusions In the immune rejection of xenotransplantation, the antibodies that mediate humoral immunity mainly originate from the immune cells in the marginal zone of the spleen and reach the immune response site after 3d, which plays an important role in cellular immunity.