Adenovirus-delivered Angiopoietin-1Treatment For Phosgene-induced Acute Lung Injury

Context:Exposure to phosgene can result in acute lung injury, leading to pulmonary edema and even death. Angiopoietin-1(Angl) is a critical factor for vascular stabilization due to its ability to reduce endothelial permeability and inflammation.Objective:In this study, the histopathological changes of the lungs after exposure to phosgene gas and the effect of Angl treatment were examined.Materials and methods:Rats were exposed to phosgene gas at8.33g/m3for5min. Angl overexpressing rats were established by an intravenous injection of adeno virus-Angl (Ad/Angl). The histological changes of the lung were examined by Haematoxylin-Eosin staining and fluorescence microscopy. The inferior lobe was used for the determination of the ratio of wet weight to dry weight of the lung. The concentration of cytokines in the serum and bronchoalveolar lavage fluid was determined by enzyme-linked immunosorbent assay.Results:The pathological analysis showed signs of inflammation and edema, evident from a significant increase in the number of leukocytes in bronchoalveolar lavage fluid and the ratio of wet to dry weight of the lungs. The lung injury induced by phosgene gas inhalation was markedly reduced after the injection of Ad/Angl. The increase of IL-1β and IL-17and decrease of VEGF in the serum and bronchoalveolar lavage fluid of phosgene-exposed animals were abolished by the administration of Ad/Angl. Discussion and conclusions:Angl has the protective effects on phosgene-induced lung injury. The adenovirus-delivered Angl may have the potential for serving as a novel approach for the treatment of the acute lung injury caused by phosgene gas inhalation in humans.