Lin L, Gu H M, Zhang W N, Zhao X N, Zhang H Y, Tang G Z, Li M Y, Zhang Z X
School of Medicine, Department of Biochemistry, Nanjing University.
Yao Xue Xue Bao. 1995 Nov;30(11):806-11.
The enhancing effects of morphine on monosodium glutamate (MSG) neurotoxicity and its blocking by naloxone were studied through morphological observation, together with detection of concentrations of intracellular free Ca2+ ([Ca2+]i) by Ca2+ indicator Fura-2/AM and lactate dehydrogenase (LDH) efflux in the bathing medium in primary cultures from 14-17 d old mouse fetal cortex. It was found that 10 min pre-incubation of young cortical neurons (7 day in vitro) with morphine 10(-7) or 10(-6) mol.L-1 substantially increased LDH release from 105.7% +/- 19.0% (treated with MSG alone) to 194.5% +/- 17.7% and 214.0% +/- 9.5% respectively after exposure to MSG 0.1 mmol.L-1, but pre-incubation with morphine (10(-7) or 10(-6) mol.L-1) plus naloxone (0.1 mmol.L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine (10(-7) or 10(-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 results suggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed by naloxone. Overloading of intracellular Ca2+ may be a simultaneous pathological mechanism underlying the neuronal damage and death that occur in excitatory toxicity.
通过形态学观察，以及使用钙离子指示剂Fura-2/AM检测原代培养的14 - 17日龄小鼠胎儿皮质细胞内游离钙离子浓度（[Ca2+]i）和培养基中乳酸脱氢酶（LDH）外流，研究了吗啡对谷氨酸（MSG）神经毒性的增强作用及其被纳洛酮阻断的情况。结果发现，将年轻的皮质神经元（体外培养7天）与10(-7)或10(-6) mol.L-1吗啡预孵育10分钟后，在暴露于0.1 mmol.L-1 MSG后，LDH释放量从单独使用MSG时的105.7% +/- 19.0%分别大幅增加至194.5% +/- 17.7%和214.0% +/- 9.5%，但与吗啡（10(-7)或10(-6) mol.L-1）加纳洛酮（0.1 mmol.L-1）预孵育后，在相同浓度MSG处理后可逆转LDH释放。吗啡（10(-7)或10(-6) mol.L-1）使[Ca2+]i略有升高。然而，当与MSG（0.1 mmol.L-1）联合使用时，吗啡使[Ca2+]i水平升高的幅度远大于单独使用MSG时。这些结果表明，吗啡显著增强兴奋性毒性神经元损伤，而纳洛酮可逆转这种损伤。细胞内钙离子超载可能是兴奋性毒性中神经元损伤和死亡同时发生的病理机制。
