Abstract：
Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care, the pathogenesis of which potentially involves altered lipid metabolism. Given the critical role of lipids in lung development and the injury response, we hypothesized that specific lipid species could serve as therapeutic agents in BPD. This study aimed to investigate the role of the lipid Phosphatidylcholine (PC) (16:0/14:0) in modulating BPD pathology and to elucidate its underlying mechanisms of action. Our approach integrated in vitro and in vivo methodologies to assess the effects of PC (16:0/14:0) on the histopathology, cellular proliferation, apoptosis, and molecular markers in lung tissue. In a hyperoxia-induced BPD rat model, we observed a reduction in alveolar number and an enlargement in alveolar size, which were ameliorated by PC (16:0/14:0) treatment. Correspondingly, in BPD cell models, PC (16:0/14:0) intervention led to increased cell viability, enhanced proliferation, reduced apoptosis, and elevated surfactant protein C (SPC) expression. RNA sequencing revealed significant gene expression differences between BPD and PC (16:0/14:0) treated groups, with a particular focus on Cldn1 (encoding claudin 1), which was significantly enriched in our analysis. Our findings suggest that PC (16:0/14:0) might protect against hyperoxia-induced alveolar type II cell damage by upregulating CLDN1 expression, potentially serving as a novel therapeutic target for BPD. This study not only advances our understanding of the role of lipids in BPD pathogenesis, but also highlights the significance of PC (16:0/14:0) in the prevention and treatment of BPD, offering new avenues for future research and therapeutic development.
摘要：
支气管肺发育不良（BPD）仍然是新生儿护理的重大挑战，其发病机制可能涉及脂质代谢的改变。鉴于脂质在肺发育和损伤反应中的关键作用，我们假设特定的脂质种类可以作为BPD的治疗药物。本研究旨在研究脂质磷脂酰胆碱（PC）（16：0/14：0）在调节BPD病理中的作用，并阐明其潜在的作用机制。我们的方法整合了体外和体内方法来评估PC（16：0/14：0）对组织病理学的影响，细胞增殖，凋亡，和肺组织中的分子标志物。在高氧诱导的BPD大鼠模型中，我们观察到肺泡数量减少和肺泡大小增大，PC（16：0/14：0）治疗改善。相应地,在BPD细胞模型中，PC(16:0/14:0)干预导致细胞活力增加，增强扩散，减少细胞凋亡，表面活性剂蛋白C(SPC)表达升高。RNA测序显示BPD和PC(16:0/14:0)处理组之间的显著基因表达差异,特别关注Cldn1（编码Claudin1），这在我们的分析中得到了极大的丰富。我们的发现表明，PC（16：0/14：0）可能通过上调CLDN1表达来防止高氧诱导的II型肺泡细胞损伤，可能作为BPD的新治疗靶点。这项研究不仅促进了我们对脂质在BPD发病机理中的作用的理解，但也强调了PC（16：0/14：0）在预防和治疗BPD中的重要性，为未来的研究和治疗发展提供了新的途径。
