缺血再灌注（I/R）后，神经细胞损伤是一个涉及众多分子过程的病理过程。在过去的十年里，有一种新的程序性细胞死亡分类被命名为铁死亡。最近的研究表明，铁死亡在多种神经疾病中起到重要作用，包括中风、癌症和神经退行性疾病。铁死亡抑制蛋白1（FSP1）在抑制铁死亡中发挥重要作用。本研究的目的是确定FSP1过度表达如何影响在氧葡萄糖缺氧/复氧（OGD/R）条件下PC12细胞的铁死亡。通过慢病毒转染技术调控FSP1的表达。采用Western blot和免疫荧光检测与铁死亡和PI3K/AKT/GSK3β信号通路相关的蛋白水平。使用适当的试剂盒确定细胞存活率。通过透射电子显微镜检查PC12细胞的线粒体结构形态。使用相关试剂盒定量检测活性氧（ROS）和丙二醛（MDA）。OGD/R诱导PC12细胞发生铁死亡，但FSP1过度表达逆转了铁死亡，并促进了细胞存活，降低了ROS和MDA含量。FSP1的表达在OGD/R0h和OGD/R6h时降低，在OGD/R24h和OGD/R48h时回升。在OGD/R诱导的铁死亡过程中，FSP1过度表达显著激活了PI3K/AKT/GSK3β通路，但LY294002削弱了FSP1过度表达的保护作用。我们的研究结果表明，FSP1的过度表达通过PI3K/AKT/GSK3β通路显著增强了对铁死亡的抵抗能力。以上结果可能为脑缺血再灌注损伤的治疗提供了新的初步线索。© 2023 Elsevier Ltd. 发表。

After ischemia and reperfusion (I/R), nerve cell damage is a pathogenic process that involves numerous molecular processes. In the last ten years, one new classification of programmed cell death is ferroptosis. More recent research has demonstrated that ferroptosis has a role in a variety of neurological disorders, including stroke, cancer, and neurodegenerative illnesses. Ferroptosis suppressor protein 1 (FSP1) plays a significant role in inhibiting ferroptosis. The purpose of this work is to determine how overexpression of FSP1 affects the ferroptosis of PC12 cells under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R). The expression of FSP1 was regulated by lentivirus transfection technology. Western blot and immunofluorescence were used to measure protein levels related to ferroptosis and the PI3K/AKT/GSK3β signal pathway. Determine cell viability using the appropriate kit. Mitochondrial structural morphology was checked by transmission electron microscopy in PC12 cells. Reactive oxygen species (ROS) and Malondialdehyde (MDA) were quantified using the relevant kits. OGD/R induced ferroptosis in PC12 cells, however, FSP1 overexpression reverses ferroptosis and promotes cell viability, lowering ROS and MDA content. The expression of FSP1 decreased in OGD/R0h and OGD/R6h and rebounded in OGD/R24h and OGD/R48h. During the processes of OGD/R-induced ferroptosis, FSP1 overexpression significantly stimulated PI3K/AKT/GSK3β pathway, but LY294002 weakens the protective effect of FSP1 overexpression. Our outcomes demonstrate that overexpression of FSP1 markedly enhances the ability to resist ferroptosis via the PI3K/AKT/GSK3β pathway. The above results may provide a new preliminary lead for the treatment of the cerebral ischemia-reperfusion injury.© 2023 Published by Elsevier Ltd.