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

质子泵抑制剂对大鼠肺移植术后闭塞性细支气管炎的预防作用

• 批准号: 11671346
• 负责人: SAITO Yukihito
• 金额: $ 2.18万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671346/
• 关键词: lung transplantation; bronchiolitis obliterans; proton pump inhibitor; リモデリング

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.

背景和目标。闭塞性细支气管炎是影响肺移植受者长期生存的最重要的并发症。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。本研究的目的是评估质子泵抑制剂在大鼠肺移植后闭塞性细支气管炎发展中的疗效。方法（实验研究1）：将供体肺从Brown Norway大鼠移植到Brown Norway大鼠（同系移植物; A组）或刘易斯大鼠（同种异体移植物; B组）。B组给予环孢霉素。方法（实验2）：将Brown Norway大鼠气管段移植到Brown Norway大鼠（同系移植物; A组）或刘易斯大鼠（同种异体移植物; B组）。将移植物植入皮下囊袋和腹部网膜包裹物中。B组给予质子泵抑制剂巴弗洛霉素A1（200μ g/kg/d），连续21天。1：移植后90天，硝基酪氨酸免疫组化染色显示移植物发生闭塞性细支气管炎。Exp. 2. B组给予质子泵抑制剂后，纤维性气道阻塞的发生受到抑制。然而，在我们的研究中，该实验模型不适于评价质子泵抑制剂的疗效，因为BO的发生率不稳定。