Aims: Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to the 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. Main Methods: 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 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. Key findings: Rats suffered from ALI after OALT, which was demonstrated with collapse of pulmonary architecture, pulmonary edema, and infiltration of inflammatory cells in alveolar and interstitial spaces, as well as increased levels of pro-inflammatory 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 with an increase in PMN apoptosis. Significance: ALI after OLT was associated with MC activation and PMN apoptosis. The ALI progression might be affected by delayed PMN apoptosis, which was related to MC activation. Induction of PMN apoptosis might alleviate ALI after OALT.

中文翻译：

---

稳定肥大细胞通过促进多形核中性粒细胞凋亡来改善原位肝移植后急性肺损伤

目的：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，以机制不明的原因导致原位肝移植（OLT）的死亡率和发病率。肥大细胞（MCs）和多形核中性粒细胞（PMNs）是ALI过程中的主要炎症细胞和参与者。本研究旨在调查OLT后MC和PMN的作用及其与ALI的潜在关系。主要方法：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。我们还评估了成年大鼠中MC的功能以及TNF-α和类胰蛋白酶对ALI和PMN凋亡的影响。测量组织学评分和炎性因子水平以及PMN凋亡。关键发现：OALT后大鼠患有ALI，其表现为肺结构崩溃，肺水肿，肺泡和间质间隙中的炎性细胞浸润以及促炎性细胞因子水平升高。口服后8小时，ALI最高。然而，当急性炎症缓解开始时，PMN细胞凋亡滞后于肺损伤，并在OALT后16小时达到最大。MC稳定，以及类胰蛋白酶和TNF-α抑制剂可显着降低肺部病理生理评分，并伴有PMN凋亡增加。意义：OLT后的ALI与MC激活和PMN凋亡相关。ALI的进展可能受到PMN凋亡延迟的影响，这与MC激活有关。诱导PMN凋亡可能减轻OALT后的ALI。