脊髓损伤后神经元铁死亡:谷胱甘肽过氧化物酶4的调控

Glutathione peroxidase 4 regulates neuronal ferroptosis after spinal cord injury

背景:铁死亡作为一种以脂质过氧化为特征的铁离子依赖性细胞死亡方式,与脊髓损伤病理生理过程密切相关。谷胱甘肽过氧化物酶4是铁死亡的重要调节因子,在脊髓损伤后神经元铁死亡的调控中有着关键作用。目的:针对谷胱甘肽过氧化物酶4在脊髓损伤后神经元铁死亡的调控作用研究进展做一综述,总结谷胱甘肽过氧化物酶4在脊髓损伤发生发展中的作用及其抑制剂的应用前景,以探索脊髓损伤新的治疗策略,同时为靶向铁死亡治疗脊髓损伤提供理论依据。方法:检索PubMed、Web of Science、CNKI及万方数据库收录的相关文献。利用Mesh检索“ferroptosis”“GPx4”“spinal cord injury”完善检索词,再通过主题词(标题/摘要)进行检索。英文检索词为:“GPx4,glutathione peroxidase 4,ferroptosis,spinal cord injury,SCI,Spinal Cord Trauma”;中文检索词为:“谷胱甘肽过氧化物酶4,铁死亡,脊髓损伤”等。检索时间为各数据库建库至2021年7月,最终纳入74篇文献进行归纳总结。结果与结论:①铁死亡作为新近发现的细胞死亡方式,已有证据表明参与到脊髓损伤病理生理过程当中。谷胱甘肽过氧化物酶4被认为是铁死亡重要的调节因子,在脊髓损伤中发挥着关键作用。②研究显示多种抑制剂及药物可通过恢复谷胱甘肽过氧化物酶4活性来抑制脂质过氧化继而调控脊髓损伤后神经元铁死亡,在多项基础研究中都显示出了改善神经功能损伤的功效,但在临床试验中仍存在一定的局限性。③因此,通过靶向铁死亡治疗脊髓损伤可能是未来研究中可进一步探索的方向。

BACKGROUND:Ferroptosis,a form of iron ion-dependent cell death characterized by lipid peroxidation,is closely related to the pathophysiological process of spinal cord injury.Glutathione peroxidase 4 is an important regulator of ferroptosis and plays a key role in the regulation of neuronal ferroptosis after spinal cord injury.OBJECTIVE:To review the research progress in the regulatory role of glutathione peroxidase 4 in neuronal ferroptosis after spinal cord injury,to summarize the effect of glutathione peroxidase 4 in the occurrence and development of spinal cord injury and its application prospects as an inhibitor,and to explore new therapeutic strategies for spinal cord injury,providing a theoretical basis for targeting ferroptosis in the treatment of spinal cord injury.METHODS:Databases of PubMed,CNKI,Web of Science and WanFang were searched for relevant literature.The search terms"ferroptosis,""GPx4,"and"spinal cord injury"were refined using Mesh,and then the search was conducted by subject terms(title/abstract).The search terms were"GPx4,glutathione peroxidase 4,ferroptosis,spinal cord injury,SCI,spinal cord trauma"in English and"glutathione peroxidase 4,ferroptosis,spinal cord injury"in Chinese.The search period was from the inception of the database to July 2021,and finally 74 papers were included for review.RESULTS AND CONCLUSION:(1)Ferroptosis,as a newly identified mode of cell death,has been shown to be involved in the pathophysiological process of spinal cord injury,and glutathione peroxidase 4 is considered to be an important regulator of ferroptosis and plays a key role in spinal cord injury.(2)Studies have shown that various inhibitors and drugs can inhibit lipid peroxidation and regulate neuronal ferroptosis after spinal cord injury by restoring glutathione peroxidase 4 activity.Efficay in improving neurological impairment has been shown in several basic studies,but limitations still exist in clinical trials.(3)Therefore,treatment of spinal cord injury by targeting ferroptosis may be a direction that can be further explored in future studies.