Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou City, People's Republic of China.
Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen City, People's Republic of China.
Am J Physiol Lung Cell Mol Physiol. 2021 Feb 1;320(2):L266-L275. doi: 10.1152/ajplung.00046.2020. Epub 2020 Nov 11.
Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to mortality and morbidity of orthotopic liver transplantation (OLT) with unclear mechanisms. Mast cells (MCs) and polymorphonuclear neutrophils (PMNs) are the main inflammatory cells and participants in the process of ALI. The present study was designed to investigate the role of MCs and PMNs and their potential relation to ALI following OLT. Rat orthotopic autologous liver transplantation (OALT) model was designed to determine lung injury at different time points after liver reperfusion. We also evaluated the function of MCs and the effect of tumor necrosis factor-α (TNF-α) and tryptase on ALI and PMN apoptosis in rats subjected to OALT. Histological scores and inflammatory factor levels as well as PMN apoptosis were measured. Rats suffered from ALI after OALT, which was demonstrated by a collapse of the pulmonary architecture, pulmonary edema, and infiltration of inflammatory cells in alveolar and interstitial spaces, as well as increased levels of proinflammatory cytokines. ALI maximized at 8 h after OALT. However, PMN apoptosis lagged behind the pulmonary injury and maximized at 16 h after OALT, when the acute inflammation resolution initiated. MC stabilization, and tryptase and TNF-α inhibitors could significantly decrease the lung pathophysiologic scores accompanied by an increase in PMN apoptosis. ALI after OALT was associated with MC activation and PMN apoptosis. ALI progression might be affected by delayed PMN apoptosis, which was related to MC activation. Induction of PMN apoptosis might alleviate ALI after OALT.
术后肺部并发症，包括急性肺损伤（ALI）和急性呼吸窘迫综合征，导致了原位肝移植（OLT）的死亡率和发病率增加，但具体机制尚不清楚。肥大细胞（MCs）和多形核粒细胞（PMN）是主要的炎症细胞，也是 ALI 过程中的参与者。本研究旨在探讨 MCs 和 PMNs 在 OLT 后 ALI 中的作用及其潜在关系。设计大鼠原位自体肝移植（OALT）模型，以确定肝再灌注后不同时间点的肺损伤。我们还评估了 MCs 的功能以及 TNF-α和胰蛋白酶对 OALT 大鼠 ALI 和 PMN 凋亡的影响。测定组织学评分、炎症因子水平和 PMN 凋亡。OALT 后大鼠发生 ALI，表现为肺结构塌陷、肺水肿和肺泡及间质炎性细胞浸润，促炎细胞因子水平升高。OALT 后 8 h 达到 ALI 高峰。然而，PMN 凋亡滞后于肺损伤，在 OALT 后 16 h 达到高峰，此时急性炎症开始消退。MC 稳定化、胰蛋白酶和 TNF-α抑制剂可显著降低肺病理生理评分，同时增加 PMN 凋亡。OALT 后 ALI 与 MC 活化和 PMN 凋亡有关。PMN 凋亡的延迟可能会影响 ALI 的进展，这与 MC 活化有关。诱导 PMN 凋亡可能减轻 OALT 后的 ALI。
