Maresin-1 alleviates lipid peroxidation-induced ferroptosis after radiation-induced brain injury in mice through the RORα/NRF2 pathway.

作者：Jiajia Duan, Yiping Wang, Jiang Enyan, Shouwu Zhu, Yang Shuai, Xiaojian Zhang, J. Juan, Fang Zhen, Zeng Jia, Wang Jikai, Yan Yang, Huiqing Li, Liu Fei · 发表于：Experimental Neurology · 年份：2025 · DOI：10.1016/j.expneurol.2025.115258 · 被引用次数：8 · 研究领域：Medicine

Ferroptosis plays a critical role in radiation-induced brain injury (RIBI). The role of Maresin-1, which has anti-inflammatory and antiferroptotic properties, in RIBI is still unclear. This study aimed to explore the effects and mechanisms of Maresin-1 on ferroptosis after RIBI in mice. A mouse model of RIBI was constructed through whole-brain irradiation. Short-term neurological functions were evaluated by the modified Garcia score and the beam balance score, and long-term neurological functions were evaluated by the Morris water maze and the rotarod test. Changes in the number of NeuN-positive neurons were detected through immunohistochemistry. The lipid peroxidation level was evaluated by detecting the contents of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione-reduced (GSH) and glutathione-oxidized (GSSG). The expression of the ferroptosis-related markers glutathione peroxidase 4 (GPX4) and cyclooxygenase 2 (COX2) was assessed via Western blotting. Adeno-associated viruses were used to knock down retinoic acid receptor-related orphan receptor alpha (RORα) or nuclear factor erythroid 2-related factor 2 (NRF2) to explore the mechanism by which Maresin-1 alleviates ferroptosis. The results showed that Maresin-1 could significantly reduce the levels of MDA, 4-HNE, GSSG, and COX2 after RIBI; increase the contents of GSH and GPX4; reduce neuronal loss in the cortex and hippocampus; and improve the short-term and long-term neurological functions of mice. After the k...