Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly found in premature infants. Excessive inflammation and oxidative stress contribute to BPD occurrence and development. Simvastatin, as an inhibitor of HMG-CoA reductase, has been reported to have antioxidative and anti-inflammatory effects. However, its effect and possible mechanisms in hyperoxia-induced lung injury are rarely reported. In this study, in vivo and in vitro experiments were conducted to investigate whether simvastatin could ameliorate hyperoxia-induced lung injury and explore its potential mechanism. For the in vivo study, simvastatin could improve alveolar development after hyperoxic lung injury and reduce hyperoxic stress and inflammation. The in vitro study revealed that simvastatin can reduce inflammation in A549 cells after high-oxygen exposure. Simvastatin suppressed NLRP3 inflammasome activation and played anti-inflammatory and antioxidant roles by increasing KLF2 (Krüppel-like factor 2) expression. In vitro experiments also revealed that these effects of simvastatin were partially reversed by KLF2 shRNA, indicating that KLF2 was involved in simvastatin effects. In summary, our findings indicate that simvastatin could downregulate NLRP3 inflammasome activation and attenuate lung injury in hyperoxia-induced bronchopulmonary dysplasia via KLF2-mediated mechanism.

Background Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants with limited treatments and poor prognosis. Damaged endothelial glycocalyx leads to vascular permeability, lung edema and inflammation. However, whether hyperoxia increases neonatal pulmonary microvascular permeability by degrading the endothelial glycocalyx remains unknown. Methods Newborn mice were maintained in 60–70% O 2 for 7 days. Protectin DX (PDX), an endogenous lipid mediator, was injected intraperitoneally on postnatal d 0, 2, 4 and 6. Lung samples and bronchoalveolar lavage fluid were taken at the end of the study. Primary human umbilical vein endothelial cells (HUVECs) were cultured in 80%O 2 . Results Hyperoxia exposure for 7 days led to neonatal mice alveolar simplification with less radial alveolar count (RAC), mean linear intercept (MLI) and mean alveolar diameter (MAD) compared to the control group. Hyperoxia exposure increased lung vascular permeability with more fluid and proteins and inflammatory factors, including TNF-α and IL-1β, in bronchoalveolar lavage fluid while reducing the heparan sulfate (HS), the most abundant component of the endothelial glycocalyx, in the pulmonary endothelial cells. PDX relieve these changes. PDX attenuated hyperoxia-induced high expression of heparanase (HPA), the endoglycosidase that shed endothelial glycocalyx, p‐P65, P65, and low expression of SIRT1. BOC‐2 and EX527 abolished the affection of PDX both in vivo and intro. Conclusion In summary, our findings indicate that PDX treatment relieves hyperoxia‐induced alveolar simplification, vascular leakage and lung inflammation by attenuating pulmonary endothelial glycocalyx injury via the SIRT1/NF‐κB/ HPA pathway.