Lipoxin A4 Ameliorates Lung Development in Neonatal Rats with Hyperoxia-induced Bronchopulmonary Dysplasia by Reducing Mitochondrial Fission

Abstract Bronchopulmonary dysplasia (BPD) is a common chronic pulmonary disease in premature infants. Hyper oxygen exposure and mechanical ventilation are common causes. The pulmonary pathological changes of BPD were mainly micro alveolar simplification and pulmonary vascular development disorder. Lipoxin A4(LXA4) is an important endogenous lipid and anti-inflammatory mediator that promotes the regression of inflammation and is referred to as the brake signal of inflammatory response. The purpose of this study was to evaluate the intervention of LXA4 on pulmonary inflammation and oxidative stress in neonates with hyperoxia lung injury and to explore the mechanism of Drp1 and NLRP3 inflammasome. A BPD model was established 7 days after neonatal rats were exposed to 85% oxygen. Rats were divided in four groups: control, hyperoxia, hyperoxia + LXA4 and hyperoxia+LXA4+Mdivi-1. Lung injury was evaluated via histological examination; lung development was assessed using morphometric analyses. Pulmonary micro vessels were tested by vWF-positive staining and Evans Blue. Expression of Drp1, NF-κB, and NLRP3 was analyzed via western blot or immunohistochemistry. Dihydroethidium (DHE) levels was examined to determine oxidative stress in vitro. We found that LXA4 significantly reduced lung injury of rats, simplified alveoli, and promoted weight gain. In addition, we found that LXA4 can reduce the protein expression of pDrp1, pNF-κB and NLRP3. Therefore, we concluded that LXA4 intervention can reduce the inflammatory response in the lungs and reduce the degree of lung injury, and through the role of NLRP3 inflammatory chrome in the hypertoxic rat BPD model.