Zhang Liang, Li Haojie, Xu Shichen, Wen Hao, Yu Chaoxiao
Department of Respiratory and Critical Care Medicine, Yantaishan Hospital, Yantai, Shandong, China.
Department of Respiratory and Critical Care Medicine, Yantai Municipal Laiyang Central Hospital, Yantai, Shandong, China.
Turk J Biol. 2024 Oct 18;49(2):138-147. doi: 10.55730/1300-0152.2732. eCollection 2025.
BACKGROUND/AIM: Acute lung injury (ALI) is a major cause of morbidity and mortality after lung ischemia-reperfusion injury (LIRI). In recent years, pulmonary ferroptosis and its associated fibrosis have been recognized as important causes of LIRI. The purpose of this study is to investigate apigenin (APG) as a potential therapeutic target for treating LIRI-induced pulmonary ferroptosis and fibrosis.
A rat model of LIRI was established and the rats were randomly divided into three groups, a sham group, a LIRI group, and an APG group. The pathological changes of the lung tissue were evaluated using hematoxylin-eosin staining and Masson's trichrome staining. Alterations in lung function were assessed using the pulmonary permeability index, myeloperoxidase, and wet-to-dry weight ratio. The pulmonary ferroptosis levels were evaluated by testing Fe, the ratio of reduced glutathione to oxidized glutathione disulfide, and malondialdehyde. Western blotting was performed to investigate the effect of APG on the expression of ferroptosis and fibrosis biomarkers in the lung tissues.
The results show that APG pretreatment relieves LIRI-induced pulmonary pathological damage and functional abnormalities in rats. In addition, APG administration can significantly improve LIRI-induced pulmonary ferroptosis and fibrosis levels. However, using Nrf2 inhibitors to block the Nrf2/HO-1/GPX4 pathway significantly reversed these therapeutic effects.
These findings suggest that APG protects against LIRI-induced ferroptosis and fibrosis of lung tissues via the activation of the Nrf2/HO-1/GPX4 axis.
背景/目的：急性肺损伤（ALI）是肺缺血再灌注损伤（LIRI）后发病和死亡的主要原因。近年来，肺铁死亡及其相关纤维化已被认为是LIRI的重要原因。本研究的目的是探讨芹菜素（APG）作为治疗LIRI诱导的肺铁死亡和纤维化的潜在治疗靶点。
建立LIRI大鼠模型，将大鼠随机分为三组，假手术组、LIRI组和APG组。采用苏木精-伊红染色和Masson三色染色评估肺组织的病理变化。使用肺通透性指数、髓过氧化物酶和湿重与干重比评估肺功能的改变。通过检测铁、还原型谷胱甘肽与氧化型谷胱甘肽二硫化物的比值以及丙二醛来评估肺铁死亡水平。进行蛋白质免疫印迹法以研究APG对肺组织中铁死亡和纤维化生物标志物表达的影响。
结果表明，APG预处理可减轻LIRI诱导的大鼠肺病理损伤和功能异常。此外，给予APG可显著改善LIRI诱导的肺铁死亡和纤维化水平。然而，使用Nrf2抑制剂阻断Nrf2/HO-1/GPX4途径可显著逆转这些治疗效果。
这些发现表明，APG通过激活Nrf2/HO-1/GPX4轴保护肺组织免受LIRI诱导的铁死亡和纤维化。
