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实验性癫痫时海马内一氧化氮合酶的变化及其与谷氨酸受体的关系

任今鹏, 夏卉莉, 程介士

上海医科大学神经生物学教研室. 上海

摘要

应用免疫组织化学方法观察了青霉素致痫时海马内神经元型一氧化氮合酶（neuronalnitricoxidesynthase,nNOS）表达的时程变化及海马内微量注射NMDA受体拮抗剂MK－801（5-methyl-10，11-dihydro-5H-dibenzo［a，d］cycloheptan-5，10-iminemaleate）和非NMDA受体拮抗剂DNQX（6，7-dinitroquinoxaline-2，3-dione）对大鼠海马内nNOS表达的影响。实验结果表明：海马内nNOS的表达在青霉素致痫4h开始增加，24h达到高峰（在齿状回已有所下降）。在青霉素致痫前分别在海马内微量注射MK-801（6μg）和DNQX（4μg），则在减弱癫痫发作的同时，海马内nNOS的表达较单纯青霉素组减少。结果提示：癫痫发作伴有脑内一氧化氮的增加，这可能与癫痫引起的损伤有关；癫痫时一氧化氮的增加受到NMDA和非NMDA受体的调节；MK-801和DNQX对神经元的保护作用可能与其对一氧化氮合酶的影响有关。

关键词： 癫痫; 海马; 神经元型一氧化氮合酶; DNQX; MK-801

Cui Hong

First Clinical Institute，China Medical University. Shenyang 110001,Liaoning, China

Abstract

The time course of alteration in neuronal nitric oxide synthase (nNOS) and the influence of glutamate receptor antagonists on immunoreactivity of nNOS were investigatedimmunohistochemically in rat hippocampus during penicillin-induced epilepsy. It was found that nNOS-like immunoreactivity in hippocampus increased at 4 h after initiation of seizure and reached a peak at 24 h. When MK-801 (6μg) and DNQX (4 μg) were injected respectively into hippocampus 20 min before admnistartion of penicillin, seizure was reduced in strength. Meanwhile, the nNOS-like immunoreactivity in hippocampus was decreased, compared with the group which were administered penicillin alone. These results suggest that the increase of nitric oxide may be related to the injury of neurons during and after epilepsy; the changes of nNOS may be related to the activity of NMDA and non-NMDA receptors. Neuron protective effect of MK-801 and DNQX may be in part mediated by nNOS.

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引用本文：

任今鹏, 夏卉莉, 程介士. 实验性癫痫时海马内一氧化氮合酶的变化及其与谷氨酸受体的关系[J]. 生理学报 1998; 50 (4): .

Cui Hong. . Acta Physiol Sin 1998; 50 (4): (in Chinese with English abstract).