mGluR5 拮抗剂SIB-1893 逆转6-OHDA抑制星形胶质细胞摄取谷氨酸的作用

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (1): 25-28.

mGluR5 拮抗剂SIB-1893 逆转6-OHDA抑制星形胶质细胞摄取谷氨酸的作用

张芸¹, 丁建花, 胡刚

南京医科大学药理学与神经生物学系, 南京 210029, 江苏;
¹江苏大学医学院药理学教研室, 镇江 212001, 江苏

收稿日期:2003-08-22 修回日期:2003-09-12 出版日期:2004-01-26 发布日期:2020-11-16
通讯作者: 胡刚,男, 博士, 教授, 博士生导师, 研究方向为神经退行性疾病的病因学与实验治疗学研究。Tel:025-6863108 　E-mail: ghu@njmu.edu.cn
作者简介:张芸, 女, 讲师, 在读硕士生。
基金资助:
国家自然科学基金项目(NO.39970846); 教育部优秀青年教师资助计划项目(2001); 教育部高等院校骨干教师资助计划项目(2001); 江苏省卫生厅自然科学基金项目(NO.H9922)

SIB-1893 reversed 6-OHDA-induced inhibitory effect on glutamate uptake of astrocytes

ZHANG Yun¹, DING Jian-Hua, HU Gang

Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
¹Department of Pharmacology, School of Medical Science, Jiangsu University, Zhenjiang 212001, Jiangsu, China

Received:2003-08-22 Revised:2003-09-12 Online:2004-01-26 Published:2020-11-16

摘要/Abstract

摘要： 目的: 研究亲代谢型谷氨酸受体5(mGluR5)拮抗剂(E)-2-甲基-6-(2-苯乙烯) 嘧啶(SIB-1893) 及6-羟基多巴胺(6-OHDA) 对星形胶质细胞摄取谷氨酸功能的影响。方法: 取新生大鼠脑星形胶质细胞作原代培养, 根据[³H] 标记的D, L-谷氨酸摄入量判断细胞的谷氨酸摄取功能。应用高效液相色谱法(HPLC) 与荧光检测器联用的方法检测培养液中的谷氨酸水平;乳酸脱氢酶(LDH) 释放法测定细胞活力。结果: 6-OHDA 呈浓度依赖性抑制星形胶质细胞谷氨酸摄取功能、降低细胞活力, 但不诱导细胞释放谷氨酸;SIB-1893 不影响正常星形胶质细胞的谷氨酸摄取量, 但可以增加6-OHDA 损伤组的谷氨酸摄取量。结论: 6-OHDA 的神经损伤机制可能与其抑制星形胶质细胞谷氨酸摄取功能有关, SIB-1893则能逆转6-OHDA 引起的谷氨酸摄取抑制效应, 具有神经保护作用。

关键词: (E)-2-甲基-6-(2-苯乙烯) 嘧啶, 6-羟基多巴胺, 星形胶质细胞, 谷氨酸, 摄取, 细胞活力

Abstract: AIM: To study the effect of (E)-2-methyl-6-(2-phenylethenyl) pyridine, the metabotropic glutamate receptor5 (mGluR5) antagonist, and 6-hydroxydopamine (6-OHDA) on astrocytic glutamate uptake activity.METHODS: Rat cortical astrocytes from 1 to 2 days old rats were separated for primary culture.Glutamate uptake activity of astrocytes was determined, using isotopic techniques, by intracellular 3H-labeled D, L-glutamate concentration. In addition, the extracellular glutamate concentration was assayed by high-performance liquid chromatography(HPLC).Cell viability was assessed with the Lactate dehydrogenase (LDH) activity released into the incubation medium.RESULTS: 6-OHDA decreased astrocytic glutamate uptake in a concentration-dependent manner, but it had no effect on inducing glutamate release from astrocytes. Cell viability was also decreased in a concentration-dependent manner while LDH activity increased. SIB-1893 had no effect on normal astrocytic glutamate uptake, but increased glutamate uptake of impaired astrocytes caused by 6-OHDA.CONCLUSION: The neurotoxic mechanism of 6-OHDA may be associated with the decrease of astrocytic glutamate uptake activity. SIB-1893 can reverse the inhibitory effect induced by 6-OHDA on astrocytic glutamate uptake and therefore have neuroprotective effects.

Key words: (E)-2-methyl-6-(2-phenylethenyl) pyridine, 6-hydroxydopamine, astrocytes, glutamate, uptake, cell viability

中图分类号:

R965

张芸, 丁建花, 胡刚. mGluR5 拮抗剂SIB-1893 逆转6-OHDA抑制星形胶质细胞摄取谷氨酸的作用[J]. 中国临床药理学与治疗学, 2004, 9(1): 25-28.

ZHANG Yun, DING Jian-Hua, HU Gang. SIB-1893 reversed 6-OHDA-induced inhibitory effect on glutamate uptake of astrocytes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(1): 25-28.

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