补体在猪到猴异种心脏移植中的作用及机理

目的 探讨补体在异种大动物猪到猴心脏移植排斥反应中的作用及机理.方法 以梅山猪为供者,中国猕猴为受者,行异种腹腔异位心脏移植.随机将受者分为3组.A组(5只):为空白对照组,受者心脏移植后不作任何处理.B组(5只):为照射预处理组,受者于心脏移植前28 d、即1.5个月龄时接受60Coγ3 Gy全身剂量照射,其余同A组.C组(8只):为照射+胸腺注射预处理组,心脏移植前21 d,将供者的脾细胞(按照5×107个/只的数量)注入受者的两侧胸腺内,其余同B组.观察心脏移植术后各组移植心的存活时间;猪对猴单向混合淋巴细胞培养的刺激效应;采用双抗体夹心法检测补体C3和CD46的血清浓度;通过流式细胞术检测受者外周血细胞表面IgM、IgG阳性细胞百分比水平.结果 A、B、C三组移植心的存活时间分别为:(36.6±5.8)h、(65.6±6.5)h和(91.1±22.8)h,C组移植心的存活时间明显延长,与A组比较,P＜0.01,与B组比较,P＜0.05.C组在猪对猴单向混合淋巴细胞反应中的刺激效应较A、B组明显下降(P＜0.01).B、C组移植前补体水平(C3)无明显变化,但随着IgM、IgG水平的上升,发生排斥反应时C3和CD46水平显著降低.C组猕猴特异性抗猪抗体IgM及IgG的上升速度均较A、B组明显延缓.结论 对受者进行异种胸腺注射联合全身照射预处理在抑制T淋巴细胞免疫及体液免疫方面有重要作用,但无法抑制异种排斥反应中补体的激活,补体通过经典途径参与了延迟性异种排斥反应的发生.

Activation of complement in the discordant heart xenotransplantation of pig to monkey model

Objective To investigate the activation of complement in the discordant heart xenotransplantation of pig to monkey model. Methods In this experiment,pigs and monkeys were,respectively,selected as donors and recipients,and divided randomly into three groups. In blank group(group A),recipients didn't accept any treatments but heart xenotransplantation. In whole-body irra diation group(group B),recipients received 3 Gy(60Co) whole-body γ-irradiation(WBI) on 28 day before transplantation. In irradiation and intrathymic injection group(group C),the monkeys were pretreated by WBI and the intrathymic injection of pig spleen cells. In every group,monkeys were subjected to heterotopic heart xenotransplantation in order to observe the survival time of cardiac xenografts and the change of C3,CIN6,IgM and IgG. Results The survival time of donor hearts in group C was significantly longer than in group A(P＜0.01). There was a significant reduction of stimulation index in group C as compared with group A in mixed lymphocyte reaction assay. After xenotransplantation, the levels of xenorecative antibody of both IgM and IgG in group C were ascended slower than in group A and group B obviously(P＜0.01). After rejection the levels of CD46 and C3 were declined greatly. Conclusions The pretreatment with intrathymic injection and WBI could induce T cell immune suppression,whereby to restrain production of elicited xenorecative antibodies of both IgM and IgG classes. However,it could not hinder activation of complement during the hyperacute rejection and consequent xenograft rejection.