Leung Jason H, Chang Jui-Chih, Bell Sadé M, Holzknecht Zoie E, Thomas Samantha M, Everett Mary Lou, Parker William, Davis R Duane, Lin Shu S
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Transpl Int. 2016 Feb;29(2):253-61. doi: 10.1111/tri.12715. Epub 2015 Dec 17.
Repetitive gastric fluid aspirations have been shown to lead to obliterans bronchiolitis (OB), but the component or components of gastric fluid that are responsible are unknown. This study investigates the role of particulates and, separately, soluble material in gastric fluid during the development of OB. Whole gastric fluid (WGF) was collected from male Fischer 344 (F344) rats and separated by centrifugation into particle reduced gastric fluid (PRGF) and particulate components resuspended in normal saline (PNS). Orthotopic left lung transplants from male Wistar-Kyoto rats into F344 rats were performed using a modification of the nonsuture external cuff technique with prolonged cold ischemia. Rats were subjected to weekly aspiration of 0.5 ml/kg of WGF (n = 9), PRGF (n = 10), PNS (n = 9), or normal saline (control, NS; n = 9) for 8 weeks following transplantation. Lung allografts treated with WGF, PRGF, or PNS developed a significantly greater percentage of OB-like lesions compared with the control. No statistical difference was observed when comparing the fibrosis grades or the percentage of OB lesions of WGF, PRGF, and PNS groups, suggesting that both soluble and insoluble components of gastric fluid can promote the development of aspiration-induced OB and fibrosis in lung allografts.
反复抽吸胃液已被证明会导致闭塞性细支气管炎(OB),但其致病的一种或多种成分尚不清楚。本研究探讨了胃液中的颗粒物质以及可溶性物质在OB发生过程中的作用。从雄性Fischer 344(F344)大鼠收集全胃液(WGF),通过离心将其分离为低颗粒胃液(PRGF)和重悬于生理盐水中的颗粒成分(PNS)。采用改良的非缝合外部袖套技术并延长冷缺血时间,将雄性Wistar-Kyoto大鼠的左肺原位移植到F344大鼠体内。移植后8周,对大鼠每周进行一次0.5 ml/kg WGF(n = 9)、PRGF(n = 10)、PNS(n = 9)或生理盐水(对照组,NS;n = 9)的抽吸。与对照组相比,接受WGF、PRGF或PNS治疗的肺移植出现OB样病变的百分比显著更高。比较WGF、PRGF和PNS组的纤维化分级或OB病变百分比时,未观察到统计学差异,这表明胃液中的可溶性和不溶性成分均可促进肺移植中抽吸诱导的OB和纤维化的发展。