Abstract
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by inflammation, often caused by prolonged hyperoxia exposure in preterm infants. Platelet-activating factor (PAF) is a potent inflammatory mediator, but its role in BPD is unclear. This study explores the therapeutic potential of the PAF receptor antagonist Ginkgolide B (GB) in hyperoxia-induced lung injury. METHODS: We observed the activation status of platelets and neutrophils in BALF（bronchoalveolar lavage fluid) of patients with BPD. The supernatant of BALF from patients was sent for protein chip detection and validated by ELISA. We also measured the levels of PAF in peripheral blood and BALF. In vitro experiments, we stimulated neutrophils with PAF to detect the expression of inflammatory cytokine genes. Finally, we established a neonatal rat model of hyperoxia-induced lung injury mimicking BPD and intervened with GB. RESULTS: We observed early activation of platelets and neutrophils in the peripheral blood of BPD patients, with elevated plasma levels of PAF and myeloperoxidase-DNA (MPO-DNA). In BALF, neutrophils showed increased CD66b and MPO expression. In vitro, PAF stimulation decreased CD62L expression on neutrophils and upregulated IL-6 mRNA. Elevated levels of PAF, IL-6, IL-8, and GM-CSF were found in BPD infants' BALF supernatant. Using animal models of BPD, we found that GB significantly reduced lung damage in hyperoxia-exposed rats. GB decreased neutrophil-derived IL-6 and downregulated key proteins in the IL-6 signaling pathway (pJak2 and pStat3). CONCLUSION: Our study demonstrates that PAF activates neutrophils and promotes their lung residence. GB effectively inhibits neutrophil-derived IL-6 and alleviates hyperoxia-induced lung damage. Targeting the PAF pathway with GB may be a promising strategy for BPD and other hyperoxia-related lung diseases.