Waaga A M, Krzymański M, Ulrichs K, Oko A, Müller-Ruchholtz W
Institute of Immunology, Christian Albrechts University, Kiel, Germany.
Arch Immunol Ther Exp (Warsz). 1996;44(2-3):143-53.
The purpose of this study was to analyse the effect of various protocols of 15-deoxyspergualin (DOS) application on skin or kidney graft survival. Following rat strain combinations were used: AS-->LEW (MHC identical/non-MHC-different) and DA-->LEW (MHC-different/non-MHC-different). Reference DOS dose was 2.5 mg/kg, i.p. It was shown that the effect of DOS depended on multiple factors, such as: type of tissue or organ, onset of treatment, drug dose and length of drug application. In skin transplantation graft survival was 32-34 days in AS-->LEW and 24-26 days in DA-->LEW. Kidney graft survived more than 150 days. DOS prolonged skin survival when the application was started earlier than day 8, whereas kidney graft survived only when DOS treatment was started not later than 3-4 days after transplantation. In skin transplantation a dose of 0.3 mg/kg had a small effect-prolongation graft survival up to 4 days. Higher doses induced longer graft survival, however, maximal survival of allogeneic skin was 22 days. In kidney transplantation a dose of 0.3 mg/kg led to prolonged graft survival-up to 150 days. Doses of 2.0-2.5 mg/kg were able to induce specific tolerance. The optimal skin or kidney graft survival was obtained when DOS was applied for 14 days. Shorter than 12-day treatment with DOS led to a shorter graft survival. When donor was pretreated with DOS prolongation of non-allogeneic graft survival was observed. Our results showed that short-term application of DOS is safe and effective. To obtain optimal DOS effect the drug application must be started directly after transplantation.
本研究的目的是分析15-去氧精胍菌素（DOS）不同应用方案对皮肤或肾脏移植存活的影响。采用了以下大鼠品系组合：AS→LEW（主要组织相容性复合体相同/非主要组织相容性复合体不同）和DA→LEW（主要组织相容性复合体不同/非主要组织相容性复合体不同）。参考DOS剂量为2.5mg/kg，腹腔注射。结果表明，DOS的效果取决于多种因素，如：组织或器官类型、治疗开始时间、药物剂量和用药时长。在皮肤移植中，AS→LEW组合的移植物存活时间为32 - 34天，DA→LEW组合为24 - 26天。肾脏移植物存活超过150天。当在第8天之前开始应用DOS时可延长皮肤移植物存活时间，而肾脏移植物仅在移植后不迟于3 - 4天开始进行DOS治疗时才能存活。在皮肤移植中，0.3mg/kg的剂量有较小效果——将移植物存活时间延长至4天。更高剂量可诱导更长的移植物存活时间，然而，同种异体皮肤的最大存活时间为22天。在肾脏移植中，0.3mg/kg的剂量可使移植物存活时间延长至150天。2.0 - 2.5mg/kg的剂量能够诱导特异性耐受。当应用DOS 14天时可获得最佳的皮肤或肾脏移植物存活效果。短于12天的DOS治疗会导致移植物存活时间缩短。当供体用DOS预处理时，可观察到非同种异体移植物存活时间延长。我们的结果表明，短期应用DOS是安全有效的。为获得最佳的DOS效果，必须在移植后立即开始用药。
