丘脑网状核尾部神经元参与丙泊酚全身麻醉机制研究

项目名称： 丘脑网状核尾部神经元参与丙泊酚全身麻醉机制研究

项目编号： No.81501190

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 焦英甫

作者单位： 上海交通大学

项目金额： 17.5万元

中文摘要： 当前，学界越来越意识到麻醉药物并非通过广泛抑制大脑功能发挥全身麻醉作用，而是有着其特定的作用核团和网络机制。正常情况下，麻醉阻断了外部信息向大脑皮层的传递，而作为内、外部信息在高级中枢上下交换的枢纽性功能核团丘脑，尤其是丘脑内部的GABA能调控区域丘脑网状核（TRN），应该在全身麻醉过程中有着重要的作用。我们前期研究发现，在TRN尾部区域微量注射静脉麻醉药丙泊酚可以直接诱导大鼠进入麻醉状态，损毁该区域神经元后，大鼠对丙泊酚敏感性显著提高，而TRN头端并无此作用，提示TRN尾部神经元可能是丙泊酚发挥全麻作用的重要靶点。本课题拟在此基础上，通过核团定位给药、在体电生理记录和脑功能成像等实验方法，进一步明确TRN尾部在丙泊酚全麻过程中的角色，分析丙泊酚对TRN尾部GABA能神经元兴奋性和突触传递活动的影响，从而提出可能的以TRN尾部神经元为始动作用核团，整个丘脑参与其中的丙泊酚全身麻醉新机制。

中文关键词： 全身麻醉；静脉麻醉药；丘脑网状核；GABAA受体；脑功能成像

英文摘要： Nowadays, accumulating research indicates that anesthetics-induced general anesthesia is not due to a global depression of the brain function, but they should act on different and specific brain regions, also neural circuits. In normal condition, anesthesia blocks the transmission of external information to the brain cortex, so the thalamus as the “hub” for ascending and descending information to and from the cortex, especially the GABAergic regulative area Thalamus Reticular Nucleus (TRN) within the thalamus, should play an important role during the general anesthesia. Our preliminary data showed that, it could induce the rats’ loss of consciousness directly through microinjection of intravenous anesthetic propofol into the caudal TRN, and the sensitivity of rats to propofol increased significantly after lesion of caudal TRN neurons with ibotenic acid, while the rostral TRN didn’t show these effects, which totally suggested us that the caudal TRN probably was the key target for propofol. According to the theories and these results, we aim to clarify the exact role of caudal TRN in propofol-induced anesthesia, and examine the effect of propofol on the excitability and synaptic transmission of GABAergic neurons within the caudal TRN in this project, with drugs microinjection, in vivo electrophysiology recording of conscious rats and functional brain imaging et al. After all, we propose that there should be a caudal TRN originated and the whole thalamus involved mechanism for propofol-induced general anesthesia.

英文关键词： General anesthesia;Intravenous anesthetic;Thalamus Reticular Nucleus;GABAA receptor;functional brain imaging