低剂量甲氨蝶呤的抗炎作用机制及其在脊髓损伤中应用

摘要

Methotrexate (MTX)has dual effects of anti-inflam-matory and immune suppression,and its pharmacological mecha-nism is complex,diverse and synergistic.This paper summari-zes the main anti-inflammatory mechanism of low-dose MTX,in-cluding inhibition of JAK/STAT pathway,inhibition of inflam-matory reaction and immune response,increasing the accumula-tion of adenosine and the function of intracellular metabolites (methotrexate polyglutamate).In addition,low-dose MTX can inhibit oxidation by decreasing the level of lipid peroxidation, suppress the inflammatory response to secondary spinal cord in-jury,reduce spinal cord ischemia reperfusion injury and neuro-pathic pain,thus playing a neuroprotective role by a series of pharmacological mechanism.The anti-inflammatory mechanism of low-dose MTX and its application in spinal cord injury were reviewed,to guide the further research on the anti-inflammatory effect of MTX,and provide a theoretical basis for new drugs for clinical treatment of spinal cord injury.%甲氨蝶呤具有抗炎和免疫抑制双重功效,其药理机制复杂、多样且相互协同.该文总结了低剂量甲氨蝶呤的主要抗炎机制,包括对JAK/STAT通路和炎症反应细胞核因子的抑制作用、增加腺苷的累积及细胞内甲氨蝶呤代谢产物(多聚谷氨酸化甲氨蝶呤)的作用等.此外,低剂量甲氨蝶呤可以通过降低脂质过氧化物水平、抑制氧化反应,抑制继发性脊髓损伤的炎症反应,减轻脊髓缺血/再灌注损伤和神经性疼痛等一系列药理机制发挥神经保护作用.作者就低剂量甲氨蝶呤的抗炎作用机制及其在脊髓损伤中的应用进行综述,旨在指导对甲氨蝶呤抗炎功效的进一步研究,为脊髓损伤的临床治疗寻找新型药物提供理论依据.