Wu Yuan, Li Binbin, Xuan Yixuan, Jiang Yu, Chen Jinping, Liao Hong, Feng Jihua, Zhang Jianfeng
Department of General Practice, The Second Affiliated Hospital of Guangxi Medical University, No 166 Daxuedong Road, Nanning, Guangxi, 530007, China.
Department of General Medicine, Hunan Provincial People's Hospital, Changsha, 410005, China.
Sci Rep. 2024 Dec 30;14(1):32149. doi: 10.1038/s41598-024-83998-w.
Chronic obstructive pulmonary disease (COPD) is a common condition that poses significant health risks to humans. Pulmonary interstitial fibrosis (PIF) often manifests in advanced stages of COPD. Fluorofenidone (AKF) has a wide range of pharmacological effects, including anti-fibrotic, antioxidant, and anti-inflammatory effects. Therefore, this study aimed to assess the role of AKF in lung injury and its underlying mechanisms. The COPD mice model was constructed by cigarette smoke (CS) combined with lipopolysaccharide (LPS) treatment. The effect of AKF on COPD mice was evaluated by lung injury, lipid peroxidation, inflammatory factors, and the expression of ferroptosis markers. Furthermore, the normal human bronchial epithelial cell line, Beas-2B, was used to verify the mechanism underlying the association between ferroptosis and inflammation. AKF attenuated the cigarette smoke (CS)/LPS-induced inflammatory response in the mouse lungs. Additionally, AKF attenuated the CS/LPS-induced fibrosis response in the mouse lungs. AKF inhibits ferroptosis in lung tissues of CS/LPS-exposed mice. Furthermore, AKF suppressed the inflammatory response and ferroptosis in CSE-treated BEAS-2B cells via NF-κB signaling pathway. AKF can function as a novel ferroptosis inhibitor by inhibiting NF-κB to inhibit airway inflammation and fibrosis, providing a scientific basis for the use of AKF to prevent the progression of COPD and pulmonary fibrosis.
慢性阻塞性肺疾病（COPD）是一种常见疾病，对人类健康构成重大风险。肺间质纤维化（PIF）常出现在COPD的晚期。氟非尼酮（AKF）具有广泛的药理作用，包括抗纤维化、抗氧化和抗炎作用。因此，本研究旨在评估AKF在肺损伤中的作用及其潜在机制。通过香烟烟雾（CS）联合脂多糖（LPS）处理构建COPD小鼠模型。通过肺损伤、脂质过氧化、炎症因子和铁死亡标志物的表达来评估AKF对COPD小鼠的影响。此外，使用正常人支气管上皮细胞系Beas-2B来验证铁死亡与炎症之间关联的潜在机制。AKF减轻了香烟烟雾（CS）/LPS诱导的小鼠肺部炎症反应。此外，AKF减轻了CS/LPS诱导的小鼠肺部纤维化反应。AKF抑制CS/LPS暴露小鼠肺组织中的铁死亡。此外，AKF通过NF-κB信号通路抑制CSE处理的BEAS-2B细胞中的炎症反应和铁死亡。AKF可通过抑制NF-κB作为一种新型铁死亡抑制剂来抑制气道炎症和纤维化，为使用AKF预防COPD和肺纤维化的进展提供科学依据。
