中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (33): 6143-6146.doi: 10.3969/j.issn.1673-8225.2011.33.016

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

致死剂量N-甲基-D-天冬氨酸中毒模型小鼠对丙泊酚的反应

王恒林1,米卫东2,王永安3,赵  从3,王卓强1   

  1. 1解放军第309医院麻醉科,北京市 100091
    2解放军总医院麻醉手术中心,北京市 100853
    3军事医学科学院毒物药物研究所,北京市 100850
  • 收稿日期:2011-02-07 修回日期:2011-03-09 出版日期:2011-08-13 发布日期:2011-08-13
  • 通讯作者: 米卫东,主任医师,教授,博士生导师。解放军总医院麻醉手术中心,北京市 100853 wdmi1962@ yahoo.com
  • 作者简介:王恒林☆,男,湖北省郧县人,医学博士,副主任医师,科副主任,主要从事临床麻醉及静脉麻醉药药理学研究。 hlin309@sina. com
  • 基金资助:

    国家自然科学基金面上项目(30400551)。

Protective effects of propofol on a mouse model of toxicity induced by lethal dose of N-methyl-D-aspartate

Wang Heng-lin1, Mi Wei-dong2, Wang Yong-an3, Zhao Cong3, Wang Zhuo-qiang1   

  1. 1Department of Anesthesiology, the 309 Hospital of Chinese PLA, Beijing 100091, China
    2Department of Anesthesiology, General Hospital of Chinese PLA, Beijing 100853, China
    3Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850
  • Received:2011-02-07 Revised:2011-03-09 Online:2011-08-13 Published:2011-08-13
  • Contact: Mi Wei-dong, Chief physician, Professor, Doctoral supervisor, Department of Anesthesiology, General Hospital of Chinese PLA, Beijing 100853, China wdmi1962@yahoo. com
  • About author:Wang Heng-lin☆, M.D., Associate chief physician, Department of Anesthesiology, the 309 Hospital of Chinese PLA, Beijing 100091, China hlin309@sina.com
  • Supported by:

    the National Natural Science Foundation of China (General Program), No.30400551*

摘要:

背景:丙泊酚具有较好的抗惊厥作用,但其作用机制尚不清楚。
目的:观察丙泊酚对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠的行为学及存活率的影响。
方法:建立N-甲基-D-天冬氨酸致死模型昆明小鼠,给药前10 min,腹腔注射丙泊酚12.5,25,50,75,100 mg/kg,观察中毒小鼠的行为学改变及存活率,阳性对照组在造模前腹腔注射非特异性的N-甲基-D-天冬氨酸受体拮抗剂地佐环平   2 mg/kg,为排除丙泊酚溶剂脂肪乳可能的作用,设定了脂肪乳组,在造模前腹腔注射等容积的脂肪乳作为对照。
结果与结论:腹腔注射N-甲基-D-天冬氨酸175 mg/kg可导致小鼠全身惊厥发生并且很快死亡,而提前给予丙泊酚12.5,25,50,75,100 mg/kg后,可见其可剂量依赖性的对抗小鼠惊厥的发生,并降低小鼠的死亡率,地佐环平(2 mg/kg)可完全预防惊厥发生,而脂肪乳不能抑制惊厥的发生,对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠无保护作用。提示丙泊酚的抗惊厥作用可能与N-甲基-D-天冬氨酸受体有关。

关键词: 丙泊酚, 抗惊厥, N-甲基-D-天冬氨酸受体, 麻醉, 组织构建, 组织工程

Abstract:

BACKGROUND: Propofol exhibits good anticonvulsive effects, but the potential mechanism remains poorly understood.
OBJECTIVE: To investigate the effects of profofol on the ethological changes and survival rate of mouse models with toxicity induced by lethal dose of N-methyl-D-aspartate (NMDA).
METHODS: Kunming mouse models of toxicity-induced by NMDA were established. Before NMDA administration, propofol was subcutaneously administered at a dose of 12.5, 25, 50, and 100 mg/kg. The ethological changes and survival rate of toxic mice were observed. The positive control group mice were subcutaneously administered nonspecific NMDA receptor antagonist MK801 (2 mg/kg). A fat milk group was set and the same amount of fat milk was subcutaneously administered as control.
RESULTS AND CONCLUSION: NMDA at a dose of 175 mg/kg resulted in general seizure, and made all mice die within 10 minutes after convulsion. When 12.5, 25, 50, 75 and 100 mg/kg propofol was intraperitoneally administrated to mice within 10 minutes before NMDA injection, convulsion rate was decreased and survival rate was increased, in a dose-dependent manner. MK801 (2 mg/kg) could completely prevent convulsion, while fat milk could not produce protective effects on lethal dose of NMDA-induced toxicity in mice. These results showed that the anticonvulsive effect of propofol is possibly related to NMDA receptor.

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