Annexin A1 peptide Ac2-26 mitigates ventilator-induced lung injury in acute respiratory distress syndrome rats by enhancing endothelial nitric oxide synthase activity

Background: Mechanical ventilation is an important therapeutic strategy for supporting patients with acute respiratory distress syndrome (ARDS). However, ventilation can exacerbate lung injury and lead to ventilator-induced lung injury (VILI). This study aimed to evalaute the effect and mechanism of Annexin A1 (AnexA1) peptide Ac2-26 on VILI in ARDS rats. Methods To evalaute the effect and mechanism of Annexin A1 (AnexA1) peptide Ac2-26 on VILI in ARDS rats, Male SD rats were anesthetized, and intubated, followed by injected with vehicle as the control S group or with lipopolysaccharides (LPS) to induce ARDS. The ARD rats were ventilated, randomized and injected intravenously with vehicle, Ac2-26 or Ac2-26 and L-NIO (an inhibitor of nitric oxide synthase) as the V, VA and VA/L groups, respectively. Their arterial blood gases were analyzed longitudinally for PaO 2 /FiO 2 ratio, and the wet-to-dry lung weights and total protein concentrations in bronchoalveolar lavage fluid (BALF) were measured. The lung injury and inflammatory factors were quantified. The oxidative stress response was measured. The impact of Ac2-26 on the LPS-related cytotoxicity against A549 cells was analyzed. Results Compared with the S group, ARDS and ventilation impaired the lung function and caused lung injury in rats. Compared with V group, Ac2-26 treatment significantly ameliorated the lung function, reduced the VILI-related alveolocapillary permeability, lung injury and endothelial/epithelial cell apoptosis, oxidative stress and inflammation in VILI rats, but promoted AKT1 expression and eNOS phosphorylation, which were partially inhibited by co-treatment with L-NIO. Moreover, Ac2-26 protected against LPS-induced apoptosis of human A549 cells in vitro . Conclusions Ac2-26 effectively mitigated the severity of VILI partially by enhancing endothelial nitric oxide synthase expression in the lung of rats.