异种反应性天然抗体在豚鼠至大鼠肝移植中的作用

Effect of xenoreactive natural antibody in the liver xenotransplantation from guinea pig to rat

目的 研究异种反应性天然抗体 (XNA)在豚鼠至大鼠异种肝移植超急性排斥反应(HAR)中的作用。方法 将实验鼠随机分成A、B、C、D组 ,每组 2 0只 ,分别为对照组、术前输注豚鼠肝细胞 (HC)组、术前连续肌注山地明 (CsA)组和术前输注HC合用CsA组。采用流式细胞仪和免疫组织化学方法检测受体体内XNA含量 ,观察了受体存活时间和移植肝组织学改变。结果 移植肝组织发生了HAR。受体体内存在XNA ,以IgM为主。术前输注HC使受体体内的抗体明显升高 ,A组IgM(单位 :平均荧光强度 ,下同 )为 74.58± 31 .75 ,B组为 40 6 .42± 1 0 8.0 2 (P <0 .0 1 ) ,而使用CsA能预防抗体爆发反应 ,C组为 48.82± 1 1 .0 4 (同B组比较 ,P <0 .0 1 )。术前输注豚鼠肝细胞合并使用CsA能延长受体存活时间 ,A组为 (1 2 4 .1 0± 33 .42 )min,D组为 (1 83 .70± 2 6 .85)min(P <0 .0 1 )。移植肝表现为肝细胞水样变性 ,肝血窦和血管扩张瘀血 ,但小叶结构完整。结论在豚鼠至大鼠异种肝移植中发生的HAR是一种强烈的免疫反应 ,其中XNA所起作用有限 ;

Objective To investigate the function of xenoreactive natural antibody (XNA) in the hyperacute rejection (HAR) of liver xenotransplantation.Methods The animals were randomly divided into 4 groups (n=20 in each): control group (group A),group B receiving donor hepatocytes infusion preoperatively,group C receiving sandimmun (CsA) intramuscular injection preoperatively and group D receiving both of the above management.The XNA was detected by the technique of immuno fluorescency and flow cytometry.The survival time and the liver histology were also observed.Results HAR occurred in the transplanted livers.The XNA was found existing in the recipients,and IgM was the main component.There was an XNA outburst in group B (IgM) as compared with that in group A (406.42± 108.02 versus 74.58±31.75,unit: mean fluorescence intensity,mfi,P<0.01),but CsA could prevent the outburst of XNA in group C,which was (48.82±11.04) mfi (compared with that in group B,P< 0.01). Though having high level of XNA,the recipients,which received both HC and CsA preoperatively,had the longest survival time.Among the 4 groups,the survival time was (124.10± 33.42) ?min in group A and (183.70± 26.85) ?min in group D (P<0.01).The histological examination of the graft revealed hydrophic degeneration of hepatocytes,sinus congestion and vessel dilatation,with intact lobular structure.Conclusion HAR occuring in the model is a severe immunological reaction,in which XNA take little effects.Preoperative infusion of donor hepatocytes and injection of CsA can prolong the survival time of the recipients.