吗啡增强谷氨酸单钠神经毒性及其作用机制  

EFFECTS OF MORPHINE ON MONOSODIUM GLUTAMATE NEUROTOXICITY AND ITS MECHANISM

作　　者：林凌[1] 顾海明[1] 张维宁[1] 赵晓宁[1] 张鹤云[1] 汤国枝[1] 李敏意 张祖暄[1] 

机构地区：[1]南京大学医学院,南京大学生化系

出　　处：《药学学报》1995年第11期806-811,共6页Acta Pharmaceutica Sinica

基　　金：江苏省自然科学基金

摘　　要：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。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%土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 of[Ca2+]i. However, when combined with MSG(0.1 mmol·L-1) morphine elevated the[Ca2+]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.

关 键 词：吗啡 谷氨酸单钠 神经 毒性 钙离子 

分 类 号：R965.3[医药卫生—药理学] R964[医药卫生—药学]