以化學及放射線治療預防異體肢體移植後移植物-宿主病之研究

Abstract

The purpose of this study is to establish a simple surgical model of limb allotransplantation in order to study the nature of graft versus host disease. Two transplantation models were developed, which included, Osteo-myo-cutaneous (OMC) transplant model and the traditional full-limb transplant model. Brown Norway(BN) to Lewis(LEW) rats combination was used in the study. Leflunomide at the dose of 10mg/kg with cyclosporine (short term:30 days, Long term: 60 days) or FK506 (lowdose: 0.1 mg/kg, high-dose: 0.5 mg/kg) /kg) were given as immunosuppresants after transplantation. After stoppING the immunosuppression agents, clinical sign of GVHD or rejection of the grafts were observed and histologically examined using ED1 monoclonal antibodies in order to investigate the macrophage activity during GVHD. Finally, we compared the GVHD after limb allotransplantation with the GVHD after clinical bone marrow transplantation and P to Fl animal model in the references. As a result, only the traditional limb transplantation model developed GVHD, two of six rats showed clinical signs including sudden weight loss, poor spirit, ocular and nasal discharge, and dyspnea. Lung and lymphoid tissues (thymus and mesenteric lymph nodes) were the major target organs in pathology, which was different from GVHD after BMT. However, some rats in the OMC model, with high dose of FK506 showed the histological but not clinical evidence of GVHD. In the observation of graft rejection, the traditional limb grafts were more easily rejected than the OMC model. And high dose FK506 combined with leflunomide gave more protection than other immunosupression protocols. The macrophage activity increased during GVHD,which is similar to the changes during GVHD after BMT.