Molecular functional evaluation of brain/spinal GABA receptor subunit in response to excitation of signal transduction

脑/脊髓 GABA 受体亚基响应信号转导激发的分子功能评估

• 批准号: 12671504
• 负责人: ITO Hitoyuki
• 金额: $ 2.18万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671504/
• 关键词: GABA a receptor; α4 subinit; vobtile anesthetics; anesthesia; brain ishemia; brain protection; C57BL; 6J; GABA_A受容体; 中大脳動脈閉塞モデル; 脳梗塞; RT-PCR; C57L; BJマウス; GABAa受容体; α4 サブユットmRNA; 即時型quontified RT-PCR; C57BL6; Tマウス; ミダゾラム; プロポフォール; ペント

By the recent research of molecular biology, the subunit of GABA receptor has been clearly analyzed and the several subclass of GABAa receptor has been evaluated. In this study, the functional role of α4 subunit of GABAa receptor on the anesthesia condition of intravenous(I.v.) anesthetic and the neuronal death induced by brain ischemia was investigated As an experimental animal, C57Bl/6J mouse which has an incomplete Willis arterial circle and shows the dissimilar pharrnacological potency to each I.v. anesthetics was used in this experiments. (1)After two dosages administrations of each I.v.anesthetic to C57BL/6J mice, I.e., midazolam, pentobarbital and propofol, the anesthesia condition was classfied into two groups, such as a complete, which means full loss of the righting reflex, and an incomplete which means half loss of the righting reflex, anesthesia conditions. In case of a complete anesthesia condition, the expression of α4 subunit of GABAa receptor mNA in the several brain regions induced by propofol was significantly higher than that induced by other I.v. anesthetics and volatile anestetic. In case of an incomplete anesthesia condition, however, α4 subunit mNA expression induced by midazolam and pentobarbital, but not propofol, was significantly higher than that seen in those complete anesthesia conditions. These results suggest that α4 subunit of GABAa receptor is more sensitive to propofol, not midazolam and pentobarbital. (2)Twenty-four hours after brain ischemia, more than 60% of brain regions were significantly damaged. However, the rich regions of α4 subunit mNA expression after brain ischemia did not show the severe damages. Thus the functional role of brain α4 subunit of GABAa receptor relates to the neuronal protections.

通过近年来的分子生物学研究，对GABA受体的亚基进行了清晰的分析，并对GABA受体的几个亚类进行了评价。本实验研究GABAa受体α4亚基在静脉麻醉药麻醉状态及脑缺血致神经元死亡中的功能作用。实验动物为威利斯动脉环不完整且对不同静脉麻醉药药理作用不同的C57Bl/6J小鼠。(1)给C57BL/6J小鼠咪达唑仑、戊巴比妥和异丙酚各给药2次后，将麻醉状态分为完全组（完全失去翻正反射）和不完全组（一半失去翻正反射）麻醉状态。在完全麻醉状态下，异丙酚诱导的GABAa受体mNA α4亚基在脑内多个区域的表达明显高于其他静脉麻醉药和挥发性麻醉药。而在完全麻醉状态下，咪达唑仑和戊巴比妥诱导的α4亚基mNA表达明显高于完全麻醉状态，异丙酚诱导的α4亚基mNA表达不明显高于完全麻醉状态。结果表明，GABAa受体α4亚基对异丙酚的敏感性高于咪达唑仑和戊巴比妥。(2)缺血24小时后，60%以上的脑区明显受损。而脑缺血后α4亚基mNA表达富集区未出现严重损伤。因此，GABAa受体脑α4亚基的功能作用与神经元保护有关。