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

Background: Although mechanical ventilation is an essential support for acute respiratory distress syndrome (ARDS), ventilation also leads to ventilator-induced lung injury (VILI). This study aimed to estimate the effect and mechanism of Annexin A1 peptide (Ac2-26) on VILI in ARDS rats. Methods Thirty-two rats were randomized into the sham (S), mechanical ventilation (V), mechanical ventilation/Ac2-26 (VA) and mechanical ventilation/Ac2-26/L-NIO (VAL) groups. The S group only received anesthesia, and the other 3 groups received endotoxin and then ventilation for 4 h. Rats in the V, VA and VAL groups received saline, Ac2-26 and A c2-26/L-NIO, respectively. The gas exchange and capillary permeability were detected. The pulmonary and systemic inflammation were investigated. The oxidative stress response was also detected. Histological injury and apoptosis in lung tissues were tested. Moreover, the epithelial cells were also cultured to detect the effect of Ac2-26 on apoptosis induced by ARDS. Results All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO 2 /FiO 2 ratio was increased, but the wet-to-dry weight ratio and protein levels in BALF were decreased in the VA group. The inflammatory cells and proinflammatory factors were reduced by Ac2-26. The oxidative stress response, lung injury and apoptosis were also decreased by Ac2-26 compared to V group. All improvements of Ac2-26 were partly reversed by L-NIO. Conclusions Ac2-26 effectively reduced VILI, improved respiratory function and alveolar-capillary permeability, ameliorated endothelial injury, inhibited oxygen stress and inflammation, and reduced lung injury and apoptosis. Ac2-26-mediated protection of VILI in ARDS rats partly depended on the endothelial nitric oxide synthase pathway.