Protectin DX Relieve Hyperoxia‐induced Lung Injury by Protecting Pulmonary Endothelial Glycocalyx

Abstract

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.

Quercetin alleviates hyperoxia‐induced bronchopulmonary dysplasia by inhibiting ferroptosis through the MAPK/PTGS2 pathway: Insights from network pharmacology, molecular docking, and experimental evaluations

“…HUVECs and BEAS‐2B were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin at 37°C in a humidified atmosphere containing 5% CO 2 . To induce in vitro hyperoxia conditions, we exposed cells to 85% O 2 based on a previous study (Liang et al., 2023). HUVECs and BEAS‐2B were pretreated with or without quercetin 2 h before exposure to hyperoxia for 12 h. Quercetin (20 μM) was dissolved in dimethyl sulfoxide (DMSO) (Liu et al., 2020).…”

IRF4-mediated Treg phenotype switching can aggravate hyperoxia-induced alveolar epithelial cell injury

“…Radial alveolar counts (RACs) and mean linear intercept (MLI) were calculated in five slides from each specimen under a light microscope at 100× magnification, by senior pathologists. For each specimen, a vertical line was drawn from the center of the respiratory bronchiole to the distal pleura under a 100× light microscope, and the number of alveoli on the line was calculated as RAC [32]. Likewise, a cross line was drawn in the middle of the same field of view, the total length of the cross (L) and the number of alveolar septa (Ns) intersecting the cross were measured, and the MLI was calculated according to the formula MLI = L/Ns [33].…”