Prophylactic effect of proton pump inhibitor in the development of bronchiolitis obliterans after lung transplantation in rats

背景和目标。闭塞性细支气管炎是影响同种异体肺移植受者存活时间的最重要的并发症。从最初的结果到最终的病理实体的演变在很大程度上是未知的。本研究的目的是评价质子泵抑制剂对大鼠肺移植后毛细支气管炎闭塞的疗效。方法(实验一)：将供体肺从棕色挪威大鼠移植到棕色挪威大鼠(同种移植；A组)或Lewis大鼠(同种异体移植；B组)；B组大鼠给予环孢菌素；两组大鼠在移植后3个不同的时间点(从移植后30、60和90天)取肺，用硝基酪氨酸进行免疫组织化学染色，以检测毛细支气管炎闭塞。A组)或Lewis大鼠(同种异体移植；B组)。移植物被植入皮下小袋和腹膜包裹中。B组给予质子泵抑制剂2 0 0μg/kg/d，连续给药2 1d。1：硝基酪氨酸免疫组织化学染色显示移植后90d同种异体移植物发生闭塞性毛细支气管炎。实验2.给予质子泵抑制剂后，B组大鼠纤维状气道闭塞的发展受到抑制。然而，在我们的研究中，这种实验模型并不适合用于评价质子泵抑制剂的疗效，因为发生BO的发生率并不稳定。

Background and Objectives. Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial isult to the final pathologic entity is largely unknow. The aim of this study was to evaluate the efficacy of proton pump inhibitor in the development of bronchiolitis obliterans after lung transplantation in rats.Methods(Experimental stydy 1) : Donor lung were transplanted from Brown Norway rats to Brown Norway rats (isografts ; group A) or to Lewis rats (allograft ; group B. Cyclosporine was administrated into rats of group B. Implanted lung in both groups were harvested at 3 different time points (from 30, 60 and 90 day after transplantation) and assessed immunohistochemical study using nitrotyrosin for detecting of bronchiolitis obliterans.Methods(Experimental stydy 2) : Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts ; group A) or to Lewis rats (allograft ; group B). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. Proton pump inhibitor (200μ g/kg/day of bafilomycin A1) was administrated into rats of group B for 21days.Results and Conclusions : Exp. 1 : Immunohistochemical staining using nitrotyrosin showed a developing of bronchiolitis obliterans in allograft 90 days after transplantation. Exp. 2. The development of fibrous airway obliteration was inhibited in group B rat which was administered proton pump inhibitor. However, This experimental model was not preferable for evaluating the efficacy of proton pump inhibitor in our study because the rate of occurrence in developing BO was not stable.