Abstract： Objective To explore the protective effect of heme oxygenase-1 (HO-1) on lung injury induced by seawater drowning in mice,so as to provide a new strategy for the treatment of lung injury induced by seawater drowning.Methods Forty-eight healthy adult male BALB/c mice were randomly divided into the normal control group (n =8),the zinc protoporphyrin (ZnPP) treatment group(n =8),the seawater drowning group (3-d,7-d and 15-d treatment) (n =24) and the seawater drowning + ZnPP treatment group (n =8).The mice were immersed in the artificial seawater with a water depth of 6 cm and water temperature of (25 ± 2) ℃ for 28 seconds.Then,the moment after the mice were taken out from the water,in-time cardio-pulmonary resuscitation was perfromed and a mouse seawater drowning model was thus established.Gross morphology of the lung tissue was observed,and lung wet/dry weight (W/D) ratio,lactate dehydrogenase (LDH) and superoxide dismutase (SOD) levels were detected accordingly.At the same time,changes in the histopathology of the pulmonary tissue,pulmonary fibrosis,apoptosis and proliferation of lung epithelial cells were also observed.HO-1 protein expression and activity in the lung tissue were measured as well.Results Three and 7 days after seawater drowning,there was pulmonary hemorrhage in the lung tissue.The lung wet/dry ratio and serum LDH level significantly increased,as compared with those of the normal control group (P ＜ 0.05),and the SOD level significantly decreased,as compared with that of the normal control group (P ＜ 0.05).Furthermore,alveolar cavity was damaged,alveolar wall thickened,red blood cells and inflammatory cells were infiltrated.HO-1 protein expression level and activity in the lung tissue significantly increased as compared with those of the normal control group (P ＜ 0.05).The expression levels of HO-1 protein in the normal control group,the 3-d and 7-d seawater drowning groups were respectively (0.313 ± 0.027),(0.604 ± 0.092) and (0.945 ± 0.252),and HO-1 activity in these groups were respectively (75.0 ± 45.6),(220.0 ± 109.5) and (350.0 ± 218.9).Fifteen days after seawater drowning,the above pathological changes in the groups significantly alleviated,and no significant differences could be noted,as compared with those of the normal control group (P ＞0.05).The HO-1 protein expression in the lung tissue was (1.367 ±0.284),which was significantly higher as compared with that of the normal control group (P ＜ 0.05),while HO-1 activity was (125.0 ±50.0),and there were no significant differences,as compared with that of the normal control group (P ＞0.05).Seven days after seawater drowning,the expression of HO-1 protein in the lung tissue for the ZnPP treatment group was (1.192 ± 0.341),which displayed no significant differences from that of the seawater drowning group (1.070 ± 0.119) (P ＞ 0.05),while HO-1 activity was (40.0 ± 22.4),which was significantly lower than that of the seawater drowning group (135.0 ± 51.8) (P ＜ 0.05).As compared with the seawater drowning group,pathological changes in the ZnPP treatment group all obviously worsened 7 days after seawater drowning (P ＞ 0.05),the pulmonary fibrosis and lung epithelial cell apoptosis increased (P ＜ 0.05),and lung epithelial cell proliferation decreased.Conclusion HO-1 could alleviate lung injury induced by seawater drowning through the access of enzyme activity,and it might play an important role in the the course of lung self-repair.