N-甲基-D-天冬氨酸型谷氨酸受体的调节与氰化物中枢毒作用

Relation between modulation of the N-methyl-D-aspartate receptor and cyanide-induced neurotoxicity

氰化物可通过间接与直接两条途径激活 (N 甲基 D 天冬氨酸型 )NMDA受体 ,首先氰化物引起的能量障碍能通过促使细胞外谷氨酸 (Glu)浓度增高和细胞内Ca2 + 稳态失调 ,间接地激活NMDA受体 ,其次氰化物可能作为NMDA受体直接的调节剂 ,通过调节NMDA受体中NR1或NR2 亚型等半胱氨酸残基的氧化还原位点 ,提高NMDA受体的活性 ,随着间接和直接NMDA受体的激活 ,产生一系列由NMDA受体介导的中枢毒作用 ,最终导致神经元细胞损伤、凋亡及死亡。

Cyanide can activate the N-methyl-D-aspartate (NMDA) receptor by two approaches directly and indirectly. Firstly cyanide-induced depletion of energy is associated with the activation of NMDA receptors indirectly by increasing extracellular glutamate (Glu) and affecting cytosolic Ca 2+ homeostatic mechanisms. Secondly most likely as a conditioner of the NMDA receptor, cyanide enhances NMDA receptors responses by modulating redox sites of cysteine residue located in the subunit NR 1 or NR 2 of the NMDA receptor. NMDA receptor-induced neurotoxicity, initiated by the direct or indirect activation of NMDA receptor, leads to neuronal injury, apoptosis or necrosis finally. Therefore, it is believed that the activation of the NMDA receptor is presumably the key event in the mechanism of cyanide-induced neuronal injures.