Annexin A1 peptide Ac2-26 mitigates ventilator-induced lung injury in acute respiratory distress syndrome rats and partly depended on the endothelial nitric oxide synthase pathway.

Abstract

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. 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 three 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/N5-(1-iminoethyl)-l-ornithine (L-NIO), respectively. All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO2/FiO2 ratio was increased, but the wet-to-dry weight ratio and protein levels in bronchoalveolar lavage fluid 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. Ac2-26 mitigates VILI in ARDS rats and partly depended on the endothelial nitric oxide synthase pathway.