激活下丘脑背内侧核区星形胶质细胞可加速七氟醚麻醉小鼠觉醒  

Activation of astrocytes in the dorsomedial hypothalamus accelerates sevoflurane anesthesia emergence in mice

作　　者：郭舒婷 曹福羊 郭永馨 李言响 郝新宇 张倬宁 周志康 仝黎 曹江北[1] GUO Shuting;CAO Fuyang;GUO Yongxin;LI Yanxiang;HAO Xinyu;ZHANG Zhuoning;ZHOU Zhikang;TONG Li;CAO Jiangbei(Department of Anesthesia,First Medical Center of Chinese PLA General Hospital,Beijing 100853,China;Department of Anesthesia,Sixth Medical Center of Chinese PLA General Hospital,Beijing 100048,China;Department of Anesthesia,71st Group Army Hospital of CPLA Army,Xuzhou 221004,China)

机构地区：[1]解放军总医院第一医学中心麻醉科,北京100853 [2]解放军总医院第六医学中心麻醉科,北京100048 [3]解放军陆军第七十一集团军医院麻醉科,江苏徐州221004

出　　处：《南方医科大学学报》2025年第4期751-759,共9页Journal of Southern Medical University

基　　金：国家自然科学基金(82271213)。

摘　　要：目的探究下丘脑背内侧核(DMH)区星形胶质细胞在七氟烷麻醉觉醒中的调节作用。方法选用42只雄性C57小鼠,随机分为6组(n=7),研究星形胶质细胞在七氟烷麻醉中的活性变化时分为EGFP组和GCaMP6组,通过钙成像技术记录星形胶质细胞的活性;研究光遗传激活DMH区星形胶质细胞对麻醉觉醒的影响时,行为学实验分为EGFP组和ChR2组;光遗传脑电记录实验分为EGFP组和ChR2组。麻醉诱导与觉醒的评判标准以翻正反射的消失与恢复为准,在2.0%七氟烷浓度下记录脑电并分析爆发抑制率(BSR),在1.5%七氟烷浓度下分析脑电功率频谱。此外,采用免疫荧光染色观察GFAP阳性细胞(星形胶质细胞)与病毒蛋白信号的共定位。结果随着七氟烷浓度的增加,DMH区星形胶质细胞的活性逐渐降低。在2.0%七氟烷麻醉中,ChR2组的觉醒时间缩短(P<0.05),光遗传激活DMH区星形胶质细胞后BSR降低(P<0.001)。在1.5%七氟烷麻醉中,光激活后ChR2组小鼠的脑电γ波增加(P<0.001),δ波减少(P<0.01)。结论光遗传激活DMH区星形胶质细胞能够促进七氟烷麻醉后的觉醒,但对麻醉诱导过程无显著调节作用。这一发现为麻醉觉醒机制的研究提供了新的视角,可能为术后快速苏醒及麻醉并发症的干预提供潜在靶点。Objective To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus(DMH)during sevoflurane anesthesia emergence.Methods Forty-two male C57BL/6 mice were randomized into 6 groups(n=7)for assessing astrocyte activation in the dorsomedial hypothalamus(DMH)under sevoflurane anesthesia.Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression,and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging.For assessing optogenetic activation of astrocytes,another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation,and sevoflurane anesthesia emergence was compared using behavioral experiments.In the remaining two groups,electroencephalogram(EEG)recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors.Anesthesia induction and recovery were assessed by observing the righting reflex.EEG data were recorded under 2.0%sevoflurane to calculate the burst suppression ratio(BSR)and under 1.5%sevoflurane for power spectrum analysis.Immunofluorescence staining was performed to visualize the colocalization of GFAPpositive astrocytes with viral protein signals.Results Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased.During 2.0%sevoflurane anesthesia,the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time(P<0.05),and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR(P<0.001).Under 1.5%sevoflurane anesthesia,optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group(P<0.01).Conclusion Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction.These findings offer new insights into the mechani

关 键 词：星形胶质细胞 下丘脑背内侧核区 七氟烷 麻醉觉醒 

分 类 号：R614[医药卫生—麻醉学]