Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Mediators Inflamm. 2020 Nov 22;2020:6705985. doi: 10.1155/2020/6705985. eCollection 2020.
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 PaO/FiO 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-B, 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 PaO/FiO and decreased wet/dry weight ratios and protein levels), ameliorated histological injury, and reduced local and systemic inflammation (downregulated proinflammatory factors and NF-B 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.
呼吸机相关性肺损伤（VILI）是需要机械通气（MV）进行呼吸支持的患者中一种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。本研究旨在确定脂氧素 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 组大鼠接受大容量 MV4 小时以模拟 VILI。通过 PaO/FiO 比值、肺湿/干重比和肺组织中的蛋白水平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-B 的表达和活性以及磷酸化肌球蛋白轻链来评估 VILI 诱导的炎症。还评估了氧化应激反应、肺组织损伤和肺组织中的细胞凋亡，并检测了凋亡蛋白的表达。与假手术组相比，MV 使所有指标都恶化。与 VILI 组相比，LX4 组肺泡毛细血管通透性明显改善（PaO/FiO 升高，湿/干重比和蛋白水平降低），组织损伤减轻，局部和全身炎症减轻（促炎因子和 NF-B 表达和活性下调）。脂氧素 A4 明显抑制氧化应激反应和细胞凋亡，并平衡肺组织中凋亡蛋白的水平。脂氧素 A4 通过抗炎、抗氧化和抗细胞凋亡作用来保护 VILI。
