谷氨酸的神经毒性作用及其作用机制  

Neurotoxicity of glutamate and its mechanism Jiang Yajun,He Jiashen.

作　　者：姜亚军[1,2] 周君富[1,2] 何家声[1,2] 丁德云[1,2] 

机构地区：[1]南京铁道医学院神经内科 [2]浙江医科大学脑血管病研究室

出　　处：《铁道医学》1998年第5期286-289,共4页Railway Medical Journal

摘　　要：目的研究谷氨酸对神经细胞的毒性作用及其作用机制。方法取体外培养的胎鼠大脑皮层神经，分组加入不同浓度的谷氨酸、Ｎ－甲基－Ｄ－天冬氨酸（ＮＭＤＡ）或海藻酸（ＫＡ），ＤＬ－２－ａｍｉｎｏ－５－ｐｈｏｓｐｈｏｎｏｖａｌｅｒｉｃａｃｉｄ（ＡＰＶ）、４－Ｈｙｄｒｏｘｙｑｕｉｎｏｌｉｎｅ－２－ｃａｒｂｏｘｙｌｉｃａｃｉｄｈｙｄｒａｔｅ（ＨＱＣＡ），作用３０ｍｉｎ，２４ｈ后测定培养液内乳酸脱氢酶（ＬＤＨ）含量，并用苔盼蓝鉴定神经细胞活性。结果与空白对照组比较，加入谷氨酸组细胞培养内ＬＨＤ以及神经细胞蓝染率均显著增加（Ｐ＜０．０１），且其程度与加入的药物剂量成正相关。谷氨酸ＬＤ５０为５１．１０±４．２９μｍｏｌ／Ｌ，与ＮＭＤＡ（６６．１７±６．２０μｍｏｌ／Ｌ）相似，但显著低于ＫＡ（１７２．８０±１６．４０μｍｏｌ／Ｌ）。ＡＰＶ或ＨＱＣＡ能显著抑制谷氨酸所致的ＬＤＨ增加。结论谷氨酸的确具有神经毒性作用。Objective To study the neurotoxicity of glutamate and its mechanism. Method In the presence or the absence of the DL-2-amino-5-phosphonovaleric acid(APV) or 4 Hydroxyquinoline-2-carboxylic acid hydrate(HQCA),the cultured neurons from fetal cortex were exposed with glutamate,NMDA or KA for 30 minutes respectively,and the lactate dehydrogenases (LDH) in the media and the cell viablity were assayed 24 hours later. Results It was found that the LDH level and the cell loss in the glutamate group were markedly higher than those in the control,which was positively related to the dosage of glutamate added.The LD 50 of the glutamate was 51.10±4.29 μmol/L,which was similar to that of NMDA(66.17±6.20 μmol/L),but markedly lower than that of KA(172.80±16.40 μmol/L).It was also found that APV or HQCA significantly inbihited LDH release induced by glutamte. Conclusion Glutamate does have neuroxicity, which may be mainly dircted by the NMDA receptors.

关 键 词：谷氨酸 神经毒性 神经元 神经递质 

分 类 号：R338[医药卫生—人体生理学]