Histological damage oflung allografts according to the magnitude of acute rejection in the reiso-transplant model

摘要背景：急性排斥反应引起的移植物损伤已被报道为心脏和肾脏移植慢性期的危险因素之一。本研究旨在阐明肺同种异体移植模型停止急性同种异体排斥反应后移植物的组织学变化。方法：将WKAH大鼠肺原位移植至F344受体。第一次同种异体移植后第3天（3A组）和第5天（5A组），将移植物再异位移植回WKAH大鼠（3RA组和5RA组）。第一次等移植后5 d （5I组），将移植物再次等移植回WKAH大鼠（5RI组）。再异位移植后30天和60天取出移植物并进行组织学评估。结果：3A和5A组出现了典型的急性同种异体移植排斥反应，再同种异体移植后这种变化有所减轻，但5RA组仍明显高于3RA和SRI组。在内膜增生方面，5RA组移植后60天的评分明显高于SRI组和3RA组。60天时，5RA组气道炎症变化明显大于3RA和SRI组。5RA和3RA组细支气管周围纤维化明显大于SRI组。结论：急性排斥反应和气道炎症与再移植前的排斥程度相关；严重急性排斥反应发生明显的内膜增生，第一次急性排斥反应后发生细支气管周围纤维化。

ABSTRACTBackground: Graft damage due to acute rejection has been reported to be one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histological changes of grafts after ongoing acute allograft rejection was discontinued in lung re-iso-transplantation models.Methods: WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (Group 3A) and 5 days (Group 5A) after the first allotransplantation, the grafts were re-iso-transplanted back into the WKAH rats (Group 3RA and Group 5RA, respectively). Five days (Group 5I) after the first isotransplantation, the grafts were re-iso-transplanted back into the WKAH rats (Group 5RI). The grafts were removed 30 and 60 days after re-iso-transplantation and assessed histologically.Results: Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-iso-transplantation, though they remained significantly greater in the 5RA group than in the 3RA and SRI groups. In intimal hyperplasia, the score of the graft 60 days after re-iso-transplantation in the 5RA group was significantly higher than in the SRI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and SRI groups at 60 days. Peribronchiolar fibrosis was significantly greater in the 5RA and 3RA groups than in the SRI group.Conclusions: Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation; significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.