Ventilator-induced lung injury (VILI) is a severe and inevitable complication in patients who require mechanical ventilation (MV) for respiratory support. Lipoxin A4 is an endogenous anti-inflammatory and antioxidant mediator. The present study determined the effects of lipoxin A4 on VILI. Twenty-four rats were randomized to the sham, VILI, and lipoxin A4 (LX4) groups. The rats in the VILI and LX4 groups received large-volume MV for 4 hours to simulate VILI. Capillary permeability was evaluated using the PaO₂/FiO₂ ratio, lung wet/dry weight ratio, and protein level in the lung. VILI-induced inflammation was assessed by measuring cytokines in serum and lung tissue, the expression and activity of NF-κB, and phosphorylated myosin light chain. The oxidative stress response, lung tissue injury, and apoptosis in lung tissue were also estimated, and the expression of apoptotic proteins was examined. MV worsened all of the indices compared to the sham group. Compared to the VILI group, the LX4 group showed significantly improved alveolar-capillary permeability (increased PaO₂/FiO₂ and decreased wet/dry weight ratios and protein levels), ameliorated histological injury, and reduced local and systemic inflammation (downregulated proinflammatory factors and NF-κB expression and activity). Lipoxin A4 notably inhibited the oxidative stress response and apoptosis and balanced apoptotic protein levels in lung tissue. Lipoxin A4 protects against VILI via anti-inflammatory, antioxidant, and antiapoptotic effects.

中文翻译：

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脂氧素 A4 减少大容量机械通气大鼠呼吸机引起的肺损伤

呼吸机诱发的肺损伤 (VILI) 是需要机械通气 (MV) 进行呼吸支持的患者的严重且不可避免的并发症。脂氧素 A4 是一种内源性抗炎和抗氧化介质。本研究确定了脂氧素 A4 对 VILI 的影响。24 只大鼠随机分为假手术组、VILI 组和脂氧素 A4 (LX4) 组。VILI和LX4组大鼠接受4小时大容量MV模拟VILI。使用PaO ₂ /FiO ₂比率、肺湿/干重比和肺中的蛋白质水平来评估毛细血管通透性。通过测量血清和肺组织中的细胞因子、NF- κ的表达和活性来评估 VILI 诱导的炎症B，和磷酸化的肌球蛋白轻链。还估计了肺组织中的氧化应激反应、肺组织损伤和细胞凋亡，并检查了细胞凋亡蛋白的表达。与假手术组相比，MV 使所有指标恶化。与 VILI 组相比，LX4 组显示出显着改善的肺泡毛细血管通透性（增加 PaO ₂ /FiO ₂并降低湿/干重比和蛋白质水平），改善组织学损伤，减少局部和全身炎症（下调促炎因子和NF- κB 表达和活性）。脂氧素 A4 显着抑制氧化应激反应和细胞凋亡，并平衡肺组织中的凋亡蛋白水平。脂氧素 A4 通过抗炎、抗氧化和抗凋亡作用防止 VILI。