Chang Jui-Chih, Leung Jason, Tang Tao, Holzknecht Zoie E, Hartwig Matthew G, Duane Davis R, Parker William, Abraham Soman N, Lin Shu S
Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pathology, Duke University Medical Center, Durham, North Carolina; Department of Surgery, Tzu Chi General Hospital, Hualien, Taiwan.
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
J Heart Lung Transplant. 2014 Jul;33(7):749-57. doi: 10.1016/j.healun.2014.03.004. Epub 2014 Mar 27.
Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown.
In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control.
The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected.
These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation.
肥大细胞与人类肺移植中的闭塞性细支气管炎（OB）有关，但其在OB发生发展中的作用尚不清楚。
在本研究中，我们使用原位大鼠肺移植模型评估肥大细胞在肺移植排斥反应中的作用，该模型利用慢性抽吸胃液来可靠地诱导OB。肺移植受体（n = 35）接受慢性抽吸胃液，其中10只同时接受肥大细胞膜稳定剂色甘酸钠治疗，16只未接受该治疗，另外9只接受慢性抽吸生理盐水作为对照。
模型中与长缺血时间相关的急性移植损伤（总缺血时间6小时；典型急性移植损伤率约30%）明显被色甘酸钠阻断，因为接受色甘酸钠治疗的动物均未观察到与急性移植损伤相关的围手术期死亡率（p = 0.045）。此外，接受色甘酸钠治疗的大鼠发生的OB病变明显少于仅接受胃液治疗的大鼠（p < 0.001），受影响气道平均减少46%。
这些发现为进一步研究色甘酸钠的作用以及肥大细胞在肺同种异体移植中的作用提供了动力。
