du Toit D F, Heydenrych J J, Smit B, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, van der Merwe E A
Surgery. 1985 Apr;97(4):447-54.
The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 X 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 X 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 X 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 X 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients. Some immunosuppressive regimens gave modest graft survival, none resulted in indefinite graft survival, and there was considerable toxicity with many of the regimens. Although CS administration alone or in combination with irradiation resulted in modest pancreatic allograft survival in this model, the place of CS combined with TBI or TLI or other chemical immunosuppressive agents remains to be defined.
本研究旨在评估单独使用环孢素（CS）、单独使用全身淋巴结照射（TLI）以及CS联合全身照射（TBI）在抑制全胰切除的远交群南非大狒狒节段性胰腺移植排斥反应中的有效性。给予25mg/kg/天和50mg/kg/天的CS，平均移植存活时间分别为21.5天和24.5天。给予85mg/kg/天的CS，移植存活时间中位数为9天。接受相同口服剂量的灵长类动物之间，CS血清谷浓度存在很大的每日波动。超过300拉德的TBI会导致不可逆的骨髓抑制。接受76拉德（38×2拉德）TBI的受体取得了一定效果，移植存活时间中位数为21天，结果与接受CS治疗的受体无差异。接受600拉德（150×4拉德）TLI的受体，胰腺移植存活时间中位数为16天。TBI联合口服CS未表现出协同或相加效应，在该模型中，单次术中供体特异性输血并未提高胰腺移植存活率。然而，在10只接受100拉德（50×2拉德）TBI并无限期口服25mg/kg/天CS的灵长类动物中，有4只血糖正常超过60天。100拉德（50×2拉德）TBI联合口服和肠外CS导致6只受体中有4只发生坏死性小肠结肠炎。一些免疫抑制方案使移植有一定存活时间，但无一能使移植永久存活，且许多方案有相当大的毒性。尽管在该模型中单独使用CS或与照射联合使用能使胰腺移植有一定存活时间，但CS联合TBI或TLI或其他化学免疫抑制剂的地位仍有待确定。
