Fahrni J A, Berry G J, Morris R E, Rosen G D
Department of Pathology, Stanford University School of Medicine, California 94305-5236, USA.
Transplantation. 1997 Feb 27;63(4):533-7. doi: 10.1097/00007890-199702270-00008.
Obliterative bronchiolitis is the major cause of long-term morbidity and mortality in heart-lung and lung transplant recipients. There is presently no completely effective therapy for the treatment of obliterative bronchiolitis. We have examined the effects of rapamycin (RPM) on the development of obliterative airway disease in murine recipients of heterotopically transplanted allograft tracheas. In this model, an untreated allograft develops almost complete occlusion of the airway lumen with fibroblastic tissue and collagen scar by day 28 after transplantation. RPM administered intraperitoneally at the time of transplantation or even as late as day 14 after transplantation markedly inhibited obliteration of the airway lumen by fibroblastic tissue. Also, RPM significantly inhibited infiltration of the graft by macrophages. In the RPM-treated animals, the airway was reconstituted with an attenuated squamous epithelium rather than a normal pseudostratified epithelium. No adverse side effects were observed with RPM doses up to 12 mg/kg/ day. These findings suggest a potential role for RPM, perhaps in combination with cyclosporine, in preventing and treating obliterative bronchiolitis in heart-lung and lung allograft recipients.
闭塞性细支气管炎是心肺移植和肺移植受者长期发病和死亡的主要原因。目前尚无完全有效的疗法来治疗闭塞性细支气管炎。我们研究了雷帕霉素（RPM）对异位移植同种异体气管的小鼠受者闭塞性气道疾病发展的影响。在这个模型中，未治疗的同种异体移植物在移植后第28天，气道腔几乎被成纤维组织和胶原瘢痕完全阻塞。在移植时甚至在移植后第14天腹腔注射RPM，可显著抑制成纤维组织对气道腔的闭塞。此外，RPM显著抑制巨噬细胞对移植物的浸润。在接受RPM治疗的动物中，气道由变薄的鳞状上皮而非正常的假复层上皮重建。高达12mg/kg/天的RPM剂量未观察到不良副作用。这些发现表明RPM可能与环孢素联合使用，在预防和治疗心肺移植和肺移植受者的闭塞性细支气管炎方面具有潜在作用。
