协调性异种移植物存活时间与受体IgM型诱生抗体水平的关系

Relationship between Xenografts Survival Time and Elicited Antibodies of IgM Isotype in Concordent Xenotransplantation

目的 采用仓鼠到大鼠移植模型 ,观察移植物存活时间与受体血清IgM型诱生抗体水平的关系。 方法 仓鼠心脏移植于SD大鼠颈部 ,按不同剂量及配对方案给予免疫抑制剂 ,单磷酸肌苷 (次黄嘌呤苷 )脱氢酶抑制剂(ERL) 10～ 30mg/(kg·d)、雷帕霉素 (RAD) 1 0～ 1 5mg/(kg·d)、环孢素A (CyA) 5～ 10mg/(kg·d)。观察移植心存活时间 ,ELISA法测定移植心被排斥时血清IgM型诱生抗体水平 ,计算两者的相关系数。 结果 对照组移植心平均存活时间为 (3 7± 1 1)d。单用ERL和CyA组移植心存活时间无延长 ,RAD组有一定的延长 (6 0± 0 9)d ,P <0 0 1;联合用药组可见移植物存活时间明显延长 (P <0 0 1) :ERL +CyA、ERL +RAD、RAD +CyA及RAD +ERL +CyA组的移植物平均存活时间分别为 (8 0± 3 5 )d、 (10 3± 4 7)d、 (12 8± 2 9)d及 (10 0± 2 2 )d。排斥时大鼠抗仓鼠IgM反应显著受抑制 ,且平均抗体水平与平均移植物存活时间呈负相关 (r =- 0 86 2 ;P <0 0 5 )。结论 仓鼠移植物存活时间与受体血清IgM型诱生抗体水平呈显著的负相关 ,ERL、RAD与CyA配合使用能有效抑制大鼠抗仓鼠IgM并明显延长异种移植物的存活时间。

Objective To investigate the correlation between cardiac xenografts survival time and serum elicited xenoreactive antibodies of the IgM isotype in a concordant xenotransplantation model.Methods Golden hamster hearts were transplanted to the cervical site of SD rats. All the immunosuppressants were given orally and daily. ERL was given at a dose of 10—30 mg/kg every day, RAD 1.0—1.5 mg/kg every day and CyA 5—10 mg/kg every day. Cadiac xonografts survival time was documented and anti-hamster IgM antibodies were evaluated by ELISA.Results In the control group, the mean survival time of the xenografts was (3.7±1.1) days. In the ERL or CyA group, the survival time of the xenografts was not prolonged, while in the RAD group, graft survival time was prolonged \[(6.0±0.9) days, P<0.01\]. The mean survival time of xenografts in the group treated with ERL+CyA, ERL+RAD, RAD+CyA and RAD+ERL+CyA was (8.0±3.5) days, (10.3±4.7) days, (12.8±2.9) days and (10.0±2.2) days, respectively, significantly prolonged (P<0.01). Rat-Anti-hamster IgM responses were significantly inhibited in RAD, CyA (10 mg/kg every day) and all combined treatment groups. There was a significant negative correlation between mean graft survival rate and mean antibody level (r=-0.862, P<0.05).Conclusion Hamster cardiac xenografts survival time have a significant correlation with rat serum IgM. EXA, ERL and RAD together or in combination with CyA can effectively inhibit the IgM immune response and therefore significantly prolong xenografts survival time.