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.

Purpose: 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 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. 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 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. Conclusion: Ac2-26 mitigates VILI in ARDS rats and partly depended on the endothelial nitric oxide synthase pathway.