Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China; Department of Orthopedics, Hefei Orthopedics Hospital, 58 Chaohu Northern Road, Hefei 238001, China.
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China.
Biomed Pharmacother. 2024 Jun;175:116734. doi: 10.1016/j.biopha.2024.116734. Epub 2024 May 15.
Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced ferroptosis and provide a novel insight for treating SCI.
脊髓损伤（SCI）是一种中枢神经系统（CNS）损伤，铁死亡正在成为治疗的有希望的靶点。α-生育酚（维生素 E，Vit E）是一种具有抗铁死亡活性的化合物。α-生育酚在 SCI 后调节铁死亡的机制尚未得到深入研究。在这项研究中，基于生物信息学分析和分子对接预测，用α-生育酚治疗 SCI 大鼠。行为测试和组织学发现表明，α-生育酚促进了 SCI 大鼠的神经功能恢复和组织修复。随后，通过免疫荧光检测和定位α-生育酚对 Alox15 和铁死亡的调节作用。在体外，α-生育酚改善了 ROS 积累、铁过载、脂质过氧化和线粒体功能障碍。在体外验证了α-生育酚对 Alox15、Ptgs2 和 4Hne 表达的影响。最后，通过突变 Alox15 的第 87 位残基，削弱了α-生育酚对 Alox15 和铁死亡的抑制作用。总之，α-生育酚可以通过下调 Alox15 来减轻 SCI 诱导的铁死亡，从而促进 SCI 大鼠的神经功能恢复。本研究的结果有助于进一步了解 SCI 诱导的铁死亡，并为治疗 SCI 提供新的思路。
