吗啡增强谷氨酸单钠神经毒性及其作用机制

用皮层神经细胞体外培养、形态学观察、单个神经细胞内游离钙检测及乳酸脱氢酶(LDH)测定等方法,观察了吗啡对谷氨酸单钠(MSG)神经毒性增强作用以及纳洛酮对吗啡作用的逆转,分析了其可能的作用机制。结果表明:吗啡能显著增强的MSG的细胞毒作用.纳络酮可逆转这种增强作用,细胞内Ca²⁺超载可能是兴奋性神经毒素引起神经元死亡的共同病理学机制。

EFFECTS OF MORPHINE ON MONOSODIUM GLUTAMATE NEUROTOXICITY AND ITS MECHANISM

The enhancing effects of morphine on monosodium glutamate (MSG) neurtotoxicity and its blocking by naloxone were studied through morphological observation,together with detectionof concentrations of intracellular free Ca²⁺(Ca²⁺]i) by Ca²⁺ indicator Fura-2/AM and lactatedehydrogenase (LDH)efflux in the bathing medium in primary cultures from 14～17 d old mouse fetalcortex, it was found that 10 min pre-incubation of young cortical neurons(7 day in,vitro )withmorphine 10-7 or 10-6mol·L^-1 substantially increased LDH release from 105.7%±19.0%(treatedwith MSG alone)to l94.5%±17.7%and 214.0%±9.5%respectively after exposure to MSG0.1mmol·L^-1, but pre-incubation with morphine(10-7 or10-6 mol·L^-1)plus naloxone (0.1mmol·L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine(10-7 or 1O-6 mol·L^-1) produced little elevation ofCa²⁺]i. However, when combined with MSG(0.1 mmol·L^-1) morphine elevated theCa²⁺]i level much more than MSG alone, These resultssuggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed bynaloxone. Overloading of intracellular Ca²⁺ may be a simultaneous pathological mechanismunderlying the neuronal damage and death that occur in excitatory toxicity.