Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Biosci Biotechnol Biochem. 2022 May 24;86(6):704-716. doi: 10.1093/bbb/zbac048.
Ferroptosis, a newly discovered iron-dependent cell death, is involved in brain ischemia-reperfusion injury. Iron scavengers or ferroptosis inhibitors could reduce infarct volume and improve neurological function in mice. Resveratrol has neuroprotective and neurorestorative effects. However, it is unclear whether resveratrol can play a neuroprotective role via inhibiting ferroptosis. Our study showed that resveratrol pretreatment had a similar effect with ferrostatin‑1, which inhibited neuronal ferroptosis-related changes, such as iron overload, damages of oxidation-reduction system, and destruction of mitochondrial structure, after oxygen-glucose deprivation/reoxygenation (OGD/R) and application of ferroptosis inducers. In addition, middle cerebral artery occlusion/reperfusion (MCAO/R) injury in vivo also induced ferroptosis, and resveratrol pretreatment could inhibit ferroptosis and reduce degenerative neurons, cerebral ischemic damage and infarction volume. Our results are the first to indicate that resveratrol pretreatment might inhibit ferroptosis induced by OGD/R and ferroptosis inducers in neurons, and MCAO/R in rats.
铁死亡是一种新发现的铁依赖性细胞死亡方式，与脑缺血再灌注损伤有关。铁清除剂或铁死亡抑制剂可减少脑缺血再灌注损伤模型中小鼠的梗死体积并改善神经功能。白藜芦醇具有神经保护和神经修复作用。然而，其是否通过抑制铁死亡发挥神经保护作用尚不清楚。本研究表明，白藜芦醇预处理可发挥与 ferrostatin-1 相似的作用，抑制神经元铁死亡相关变化，如氧葡萄糖剥夺/复氧（OGD/R）和铁死亡诱导剂处理后铁过载、氧化还原系统损伤和线粒体结构破坏。此外，体内大脑中动脉闭塞/再灌注（MCAO/R）损伤也可诱导铁死亡，白藜芦醇预处理可抑制铁死亡并减少变性神经元、脑缺血损伤和梗死体积。本研究结果首次表明，白藜芦醇预处理可能抑制 OGD/R 和铁死亡诱导剂诱导的神经元铁死亡以及大鼠 MCAO/R 中的铁死亡。
