Ferroptosis is characterized by excessive accumulation of iron and lipid peroxides, which are involved in ischemia, reperfusion-induced organ injury, and stroke. Propofol, an anesthetic agent, has neuroprotective effects due to its potent antioxidant, anti-ischemic, and anti-inflammatory properties. However, the relationship between propofol and ferroptosis is still unclear. In the current study, we elucidated the role of ferroptosis in the neuroprotective effect of propofol in mouse brains subjected to cerebral ischemia reperfusion injury (CIRI). Ferroptosis was confirmed by Western blotting assays, transmission electron microscopy, and glutathione assays. Propofol regulated Nrf2/Gpx4 signaling, enhanced antioxidant potential, inhibited the accumulation of lipid peroxides in CIRI-affected neurons, and significantly reversed CIRI-induced ferroptosis. Additionally, Gpx4 inhibitor RSL3 and Nrf2 inhibitor ML385 attenuated the effects of propofol on antioxidant capacity, lipid peroxidation, and ferroptosis in CIRI-affected neurons. Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with CIRI. Propofol protected against CIRI-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. These findings may contribute to the development of future therapies targeting ferroptosis induced by CIRI.

铁死亡的特征是铁和脂质过氧化物的过度积累，这与缺血、再灌注引起的器官损伤和中风有关。丙泊酚是一种麻醉剂，由于其有效的抗氧化、抗缺血和抗炎特性而具有神经保护作用。然而，丙泊酚与铁死亡之间的关系仍不清楚。在当前的研究中，我们阐明了铁死亡在丙泊酚对遭受脑缺血再灌注损伤 (CIRI) 的小鼠大脑的神经保护作用中的作用。通过蛋白质印迹分析、透射电子显微镜和谷胱甘肽分析证实了铁死亡。丙泊酚调节 Nrf2/Gpx4 信号，增强抗氧化能力，抑制 CIRI 影响的神经元中脂质过氧化物的积累，并显着逆转 CIRI 诱导的铁死亡。此外，Gpx4 抑制剂 RSL3 和 Nrf2 抑制剂 ML385 减弱了异丙酚对受 CIRI 影响的神经元的抗氧化能力、脂质过氧化和铁死亡的影响。我们的数据支持异丙酚对铁死亡的保护作用，铁死亡是 CIRI 小鼠细胞死亡的原因。异丙酚部分通过调节 Nrf2/Gpx4 信号通路来防止 CIRI 诱导的铁死亡。这些发现可能有助于开发针对 CIRI 诱导的铁死亡的未来疗法。异丙酚部分通过调节 Nrf2/Gpx4 信号通路来防止 CIRI 诱导的铁死亡。这些发现可能有助于开发针对 CIRI 诱导的铁死亡的未来疗法。异丙酚部分通过调节 Nrf2/Gpx4 信号通路来防止 CIRI 诱导的铁死亡。这些发现可能有助于开发针对 CIRI 诱导的铁死亡的未来疗法。