雷抑素预防大鼠肾移植排斥反应的实验研究

INHIBITION OF XENOGRAFT REJECTION BY LEFLUNOMIDE IN HAMSTER-TO-RAT KIDNEY TRANSPLANTATION

目的 :了解新型免疫抑制剂雷抑素 (Lef)在以金黄仓鼠为供体 ,SD大鼠为受体的异种肾移植中的抗排斥作用。 方法 :2 0只异位肾移植受鼠随机分为 4组 (每组 5只 )。对照组 :无免疫抑制治疗 ;环孢素A(CsA)组 :给予CsA 10mg/ (kg·d) ;Lef组 :给予Lef10mg/ (kg·d) ;Lef+CsA组 :给予Lef和CsA各 10mg/ (kg·d)。观察移植肾存活时间、病理变化 ,测定受鼠血清抗仓鼠淋巴细胞毒性抗体。 结果 :对照组和CsA组移植肾分别存活 5 2± 1 5天和 5 6± 0 9天 ,排斥时抗体滴度迅速上升达 1∶10 2 4,两组间差异不显著。Lef组 (38 2± 16 6天 )和Lef +CsA组(4 7 0± 13 5天 )存活时间与对照组和CsA组差异非常显著 ,Lef+CsA组仅见肾小管变性和少量淋巴细胞浸润。Lef组抗体滴度排斥时轻度升高达 1∶2 5 6 ,Lef+CsA组抗体滴度被稳定地抑制在 1∶6 4以下。 结论 :Lef可明显延长接受金黄仓鼠供肾的SD大鼠移植肾存活时间 ,并抑制诱发高滴度抗仓鼠淋巴细胞毒性抗体的生成。 10mg/ (kg·d)Lef和 10mg/ (kg·d)CsA联用可获得协同作用。

The aim of this study is to investigate the anti-rejection effect of a novel immunosuppressant leflunomide (Lef)in concordant kidney xenotransplantation. METHODOLOGY Twenty heterotopic kidney transplantations from golden hamsters to SD rats were performed.The recipients were divided randomly into four groups( n= 5).Control:No immunosuppressant;CsA group:CsA 10 mg/(kg·d);Lef group:Lef 10 mg/(kg·d);and CsA+Lef group:CsA and Lef 10 mg/(kg·d) respectively.The graft survival time,graft pathological features and serum titer of anti-hamster lymphocytotoxic antibody were compared. RESULTS The mean graft survival time in control group and CsA group were 5 2±1 5 days and 5 6±0 9 days respectively.The rejected xenografts showed denaturation,necrosis,edema and hemorrhage,small vessel thrombosis and neutrophil infiltration.The titer of anti-hamster lymphocytotoxic antibody increased rapidly to 1∶1024 when rejection occurred.There were no difference between the control group and the CsA group in graft survival time,pathological features and antibody titer.The graft survival time in Lef group(38 2±16 6 days)and CsA+Lef group(47 0±13 5 days)were prolonged significantly as compared to those in control group and CsA group.Only mild or moderate denaturation of tubule and small amounts of infiltrating lymphocytes were found in CsA+Lef group.The antibody titers in CsA+Lef group were maintained below level of 1∶64 throughout the observation,while mildly elevated titers(1∶256)were observed in rats with rejection in Lef group. CONCLUSION Lef is effective in prolonging graft survival time in hamster-to-rat kidney xenotransplantation by inhibiting production of induced lymphocytotoxic antibody.