神经生长因子在培养的大鼠脑皮质神经细胞抑制谷氨酸引起的一氧化氮合酶基因表达及一氧化氮释放

中国临床药理学与治疗学 ›› 1998, Vol. 3 ›› Issue (4): 241-244.

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神经生长因子在培养的大鼠脑皮质神经细胞抑制谷氨酸引起的一氧化氮合酶基因表达及一氧化氮释放

吴俊芳, 王平¹, 张均田

中国医学科学院药物研究所药理室,北京 100050;
¹江西省上饶地区第二人民医院

收稿日期:1998-08-31 修回日期:1998-09-18 出版日期:1998-12-26 发布日期:2020-12-01
作者简介:吴俊芳,女,34岁,副研究员,医学博士,博士后,主要研究方向:神经药理学;张均田,男,66岁,教授,中国药理学会理事长,主要从事神经药理学研究。

Nerve growth factor prevents nitric oxide release and nitric oxide synthase gene expression induced by glutamate in primary cortical cultures of fetal rats

WU Jun-Fang, WANG Ping¹, ZHANG Jun-Tian

Dept.of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences ＆ Chinese Union Medical University,Beijing 100050;
¹Shangrao Secondary Hospital

Received:1998-08-31 Revised:1998-09-18 Online:1998-12-26 Published:2020-12-01

摘要/Abstract

摘要： 目的研究神经生长因子(NG F)对谷氨酸引起的原代培养的神经细胞一氧化氮(NO)释放和原生型一氧化氮合酶(cNOS)基因表达的影响。方法测定神经细胞的生存力来分析NGF的作用。用荧光分析法测定细胞上清液NO 含量,用No rthern blot 杂交法观察cNOSmRNA表达。结果谷氨酸(0 .5~ 2 .0mmol/L)引起神经元大量死亡,NO 过量释放。NOS 抑制剂L-NAME (100μmol/L)及NGF (100μg/L)显著抑制谷氨酸引起NO 释放及细胞死亡。NGF (50,100μg /L)显著降低谷氨酸引起的cNOSmRNA 的高表达。结论 NO 介导了谷氨酸对皮质神经元的毒性,NG F 通过抑制cNOS 活性,降低NO 释放来保护大脑皮质细胞对抗谷氨酸毒性。

关键词: 神经生长因子, 大脑皮质, 细胞培养, 谷氨酸, 一氧化氮, 一氧化氮合酶

Abstract: Aim To study the effects of nerve growth factor (NGF) on nitric oxide (NO ) release and constitutive nitricoxide synthase (cNOS) geneexpression induced by glutam ate(Glu) in cortical neuronal cuItures.Methods Neuron viability was measured to assay NGF effect.NO content and the expression of cNOS mRNA w ere determined by fluo-rometric method and Northe rn blotting respectively.Results Glu (0.5~2.0 mmolL)induced a marked increase of neuronal death and NO content in cultured cerebral cortical neurons.L-NAME (100μmol/L) and NGF (100μg/L) signifi cantly inereased neuronal surviving and decreased NO release.Hemolglobin (Hb),which binds NO,completely prevented Gluinduced cell death and NO release at 500 pμmoY L.NGF (50,100μg/L)sigmificantly inhibited cNOS m RNA expression induced by Glu (0.5 mmoYL).Conclusion NO mediates Gluneurotoxicity in cortical neuronal cultures and NGF protects the neurons against Gluneurotoxicity viainhibiting the activity of cNOS and the release of NO.

Key words: nerve growth factor, cerebral cortex, cell, culture, glutamie acid, nitric oxide, nitric oxide synthase

中图分类号:

R969.2

吴俊芳, 王平, 张均田. 神经生长因子在培养的大鼠脑皮质神经细胞抑制谷氨酸引起的一氧化氮合酶基因表达及一氧化氮释放[J]. 中国临床药理学与治疗学, 1998, 3(4): 241-244.

WU Jun-Fang, WANG Ping, ZHANG Jun-Tian. Nerve growth factor prevents nitric oxide release and nitric oxide synthase gene expression induced by glutamate in primary cortical cultures of fetal rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 1998, 3(4): 241-244.

参考文献

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神经生长因子在培养的大鼠脑皮质神经细胞抑制谷氨酸引起的一氧化氮合酶基因表达及一氧化氮释放

Nerve growth factor prevents nitric oxide release and nitric oxide synthase gene expression induced by glutamate in primary cortical cultures of fetal rats

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