氯胺酮的神经保护作用及其对p38 蛋白磷酸化激活的影响

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (1): 15-19.

氯胺酮的神经保护作用及其对p38 蛋白磷酸化激活的影响

吴兴军, 陈红专, 陆阳

上海第二医科大学药物研究所, 上海 200025

收稿日期:2004-10-26 修回日期:2004-12-07 出版日期:2005-01-26 发布日期:2020-11-19
通讯作者: 陆阳, 男, 教授, 博士生导师, 研究方向:生物活性物质的化学及药理研究。Tel:021-63846590-776466 E-mail:huaxue@shsmu.edu.cn
作者简介:吴兴军, 男, 讲师, 博士研究生。Tel:021-63846590-776450 E-mail:wuxingjun2003@163.com
基金资助:
国家自然科学基金项目(No30371731);上海第二医科大学-上海交通大学联合科研基金项目(No2003HZJJ002);上海市教委学科建设专项基金项目(NoJY2001)

Effects of ketamine on neuroprotection and phospho-p38 protein activation induced by oxygen-glucose deprivation in rat hippocampal slices

WU Xing-jun, CHEN Hong-zhuan, LU Yang

Institute of Drug Research, Shanghai Second Medical University, Shanghai 200025, China

Received:2004-10-26 Revised:2004-12-07 Online:2005-01-26 Published:2020-11-19

摘要/Abstract

摘要： 目的: 研究NMDA 受体拮抗剂氯胺酮对大鼠海马脑片缺糖缺氧(OGD) 损伤的神经保护作用及其对p38 蛋白磷酸化激活的影响。方法: 采用大鼠海马脑片体外OGD 损伤模型, TTC 染色抽提法观察氯胺酮对海马脑片OGD 损伤时的神经保护作用, 免疫印迹法研究“缺血再灌注”不同时间大鼠海马脑片中p38 磷酸化激活变化情况, 以及氯胺酮对p38 磷酸化激活的影响。结果: 氯胺酮显著抑制海马脑片OGD 损伤所致的A 值降低, p38 蛋白在缺血再灌注后磷酸化激活增加, 再灌注15 min 后开始上升, 2 h仍可见持续表达。氯胺酮剂量为5、10 μmol·L^-1时,能显著抑制p38 蛋白磷酸化激活(P <0.05) 。结论: 氯胺酮具有一定的神经保护作用, 其保护作用可能与抑制海马神经元p38 蛋白的磷酸化激活有关。

关键词: 脑片, 缺血再灌注, 氯胺酮, p38, 免疫印迹法

Abstract: AIM: To investigate the effects of NMDA receptor antagonist ketamine on neuroprotection and the activation of phospho-p38 protein induced by oxygen-glucose deprivation (OGD) in the rat hippocampal slices. METHODS: The OGD model of rat hippocampal slice in vitro was used for the research.The neuroprotective effects of ketamine on the OGD injury of rat hippocampal slices were assessed by 2, 3, 5-triphenyl-tetrazolium chloride (TTC) staining.The changes of phospho-p38 protein level in the hippocampus during ischemia-reperfusion and the effects of ketamine on the phospho-p38 protein activation were examined by Western blot.RESULTS: Ketamine significantly inhibited the decrease of OD in brain slices by TTC staining.The activation of phospho-p38 protein increased after reperfusion 15 min, and it consistently expressed at 2 h.Ketamine (5 and 10 mol·L^-1) markedly inhibited the activation of phospho-p38 protein (P <0.05).CONCLUSION: Ketamine shows the neuroprotective effect related to the inhibition of activation of phospho-p38 protein induced by oxygen-glucose deprivation(OGD) in the rat hippocampal slices.

Key words: brain slice, ischemia-reperfusion, ketamine, p38, Western blot

中图分类号:

R971.3

吴兴军, 陈红专, 陆阳. 氯胺酮的神经保护作用及其对p38 蛋白磷酸化激活的影响[J]. 中国临床药理学与治疗学, 2005, 10(1): 15-19.

WU Xing-jun, CHEN Hong-zhuan, LU Yang. Effects of ketamine on neuroprotection and phospho-p38 protein activation induced by oxygen-glucose deprivation in rat hippocampal slices[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(1): 15-19.

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