Relaxin‐2 Alleviates Hyperoxia‐Induced Acute Lung Injury in Neonatal Rats by Inhibiting TLR4/NF‐κB

作者：Mei Yang, Qian Liu, Aili Xuan · 发表于：Chemical Biology & Drug Design · 年份：2025 · DOI：10.1111/cbdd.70140 · 被引用次数：1 · 研究领域：Pregnancy-related medical research、Neonatal Respiratory Health Research、Injury Epidemiology and Prevention

ABSTRACT Hyperoxia‐induced acute lung injury (ALI) in neonates is driven by oxidative stress and inflammation. This study aims to evaluate the efficacy and underlying mechanisms of Relaxin‐2 (RLX‐2) in a neonatal rat model of hyperoxia‐induced ALI. Neonatal Wistar rats were exposed to 90% O 2 for one week and treated with RLX‐2 (0.5 mg/kg/day) via an osmotic pump. Methods included histopathology (hematoxylin–eosin staining), bronchoalveolar lavage fluid (BALF) analysis, Enzyme‐Linked Immunosorbent Assay (ELISA) for interleukin‐1β (IL‐1β), monocyte chemoattractant protein‐1 (MCP‐1), and tumor necrosis factor‐α (TNF‐α), oxidative stress markers [malondialdehyde (MDA) and superoxide dismutase (SOD)], and Western blotting for Toll‐like Receptor 4 (TLR4), Nuclear Factor‐kappa B (NF‐κB), and Sirtuin 1 (SIRT1). Human alveolar epithelial cells (HPAEpiCs) underwent assays using Cell Counting Kit‐8 (CCK‐8), 2′,7′‐Dichlorofluorescin diacetate (DCFH‐DA), and quantitative real‐time polymerase chain reaction (qRT‐PCR). RLX‐2 mitigated alveolar damage and inflammatory infiltration in neonatal rats with hyperoxia‐induced acute lung injury. It decreased cytokine levels, reduced MDA levels, and enhanced SOD activity, thereby alleviating oxidative stress. RLX‐2 suppressed TLR4/NF‐κB signaling by reducing p65 and Myeloid Differentiation Primary Response 88 (MyD88) expression and upregulated SIRT1. SIRT1 silencing abolished RLX‐2's effects, confirming its role in attenuating OS and inflammation. ...