铁死亡在创伤性脊髓损伤中作用的研究进展

Traumatic spinal cord injury (SCI) is a serious central nervous system traumatic disease with a high mortality rate and a high disability rate, bringing a heavy economic burden to individuals, families and society, and there is still no effective repair solution at present. The imbalance of the microenvironment after SCI and the massive death of nerve cells in the acute phase are important reasons why SCI is difficult to repair. Therefore, interfering with the cell death pathway is one of the main strategies for repair. The programmed cell death pathways found in SCI mainly include apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis. Although apoptosis and autophagy are currently the most studied death pathways in SCI, the death pathway that dominates the massive death of nerve cells in the acute phase has not been identified, and the mechanism of action of the death pathway involved in the post-injury cascade inflammatory response also urgently needs to be elucidated. Ferroptosis is a newly named iron-dependent programmed death mode in 2012, and its important role in central nervous system degeneration and traumatic injury has been increasingly discovered and is one of the important ways of nerve cell death. Some scholars have found evidence at the morphological, biochemical and molecular levels of the existence of ferroptosis in SCI during the pathological process of SCI, revealing that ferroptosis is involved in the secondary injury of spinal cord tissue after SCI, and the ferroptosis inhibitors deferoxamine and SRS16 - 86 repair SCI by interfering with the ferroptosis pathway. At present, many ferroptosis inhibitors found in vitro experiments have a neuroprotective effect, especially a repair effect in SCI, but the mechanism of action of inhibiting the ferroptosis pathway in vivo needs to be further verified. The research on ferroptosis provides a new theoretical basis and a new repair strategy for the pathological mechanism of SCI, and also provides new clues for clarifying the pharmacological mechanism of lipid peroxidation scavengers that have been reported to have a repair effect on SCI. The author reviews the research progress of ferroptosis in traumatic SCI and looks forward to the problems worthy of further research in this field.

创伤性脊髓损伤(spinal cord injury, SCI)是一种高死亡率及高致残率的严重中枢神经创伤性疾病,给个人、家庭及社会带来沉重的经济负担,目前仍没有有效的修复方案。SCI后微环境失衡,神经细胞在急性期大量死亡是SCI难以修复的重要原因,因此干预细胞死亡通路是修复的主要策略之一。在SCI中发现的细胞程序性死亡通路主要有凋亡、自噬、焦亡(pyropsis)、坏死性凋亡(necroptosis)和铁死亡(ferroptosis)。虽然目前凋亡和自噬是SCI中研究最多的死亡途径,但主导急性期神经细胞大量死亡的死亡通路尚未明确,参与损伤后级联炎症反应的死亡通路作用机制也亟待阐明。铁死亡是2012年新命名的一种铁依赖的程序性死亡方式,其在中枢神经退变和创伤性损伤的重要作用被日渐发现,是神经细胞死亡的重要方式之一。有学者在SCI病理过程中发现铁死亡在SCI中存在的形态学、生化以及分子水平的证据,揭示铁死亡参与SCI后脊髓组织的继发性损伤,且铁死亡抑制剂去铁胺和SRS 16-86通过干预铁死亡通路修复SCI。目前很多体外实验发现的铁死亡抑制剂具有神经保护作用,特别是在SCI中有修复作用,然而其体内抑制铁死亡通路的作用机制有待进一步验证。铁死亡的研究为SCI病理机制提供了新的理论依据和新的修复策略,也为阐明先前被报道有修复SCI作用的脂质过氧化清除剂的药理机制提供了新的线索。笔者对铁死亡在创伤性SCI中的研究进展进行综述,并展望本领域值得进一步研究的问题。