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

近年来，通过分子生物学的研究，对GABA受体的亚基进行了清晰的分析，并对GABA α受体的几个亚类进行了评价。本研究旨在探讨GABA α受体α4亚单位在静脉麻醉中的作用。研究麻醉剂和脑缺血诱导的神经元死亡作为实验动物，在该实验中使用C57 B1/6 J小鼠，其具有不完整的Willis动脉环，并且对每种静脉内麻醉剂显示出不同的药理学效力。（1）对C57 BL/6 J小鼠静脉注射两次每种麻醉剂后，即，咪达唑仑、戊巴比妥和丙泊酚，将麻醉条件分为两组，例如完全麻醉条件（其意味着翻正反射完全丧失）和不完全麻醉条件（其意味着翻正反射一半丧失）。在完全麻醉状态下，异丙酚诱导的几个脑区GABA α受体mNA α4亚单位的表达显著高于其他静脉麻醉药和挥发性麻醉药诱导的表达。然而，在不完全麻醉条件下，咪达唑仑和戊巴比妥诱导的α4亚基mNA表达显著高于完全麻醉条件下的表达，而丙泊酚则无此作用。提示GABA α受体α4亚单位对异丙酚敏感，而对咪唑安定和戊巴比妥敏感。（2）脑缺血后24 h，60%以上的脑区明显受损。但脑缺血后α4亚基mNA表达丰富的区域并未出现严重损伤。脑GABA α受体α4亚单位的功能作用与神经元保护有关。

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.