基底前脑γ-氨基丁酸能神经元对右美托咪定镇静作用的影响  

Influence of Basal Forebrain γ-Aminobutyric Acid Neurons on the Sedative Effect of Dexmedetomidine

作　　者：卢俊李 刘培昌 陈星羽 LU Jun-li;LIU Pei-chang;CHEN Xing-yu(Fujian Medical University Union Hospital,Fuzhou 350001,China;Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学附属协和医院,福建福州350001 [2]福建医科大学,福建福州350001

出　　处：《海峡药学》2022年第11期18-23,共6页Strait Pharmaceutical Journal

基　　金：2020年福建省卫生健康青年科研课题(2020QNA037)。

摘　　要：目的 探究基底前脑γ-氨基丁酸能神经元对右美托咪定(Dex)镇静作用的影响。方法 使用光纤光度法测定镇静前后小鼠基底前脑γ-氨基丁酸能神经元活性变化;用光遗传学手段激活基底前脑γ-氨基丁酸能神经元,并通过刺激前后脑电图与旷场运动距离估计镇静深度的改变。结果 (1)光纤记录实验中,腹腔注射Dex(40μg·kg^(-1))后,Ca^(2+)信号较给药前显著降低(P<0.01),而NS组无明显变化(P>0.05);(2)光遗传实验脑电图能谱分析显示,光激活基底前脑γ-氨基丁酸能神经元时δ波占比较刺激前显著下降(P<0.001),θ波占比无明显变化(P>0.05),α波占比较刺激前有所上升(P<0.05),β波占比显著上升(P<0.0001);(3)光遗传激活后,小鼠在旷场中的运动量显著上升(P<0.01)。结论 右美托咪定可抑制小鼠基底前脑γ-氨基丁酸能神经元活性;激活基底前脑γ-氨基丁酸能神经元可降低小鼠的镇静深度。OBJECTIVE To investigate the effect of basal forebrain γ-aminobutyric acid neurons on the sedative effect of dexmedetomidine(Dex).METHODS The activity of γ-aminobutyric acid neurons in the basal forebrain of mice was measured by optical fiber photometry before and after sedation.The basal forebrain γ-aminobutyric acidergic neurons were activated by photogenetics, and the changes of sedation depth were estimated by electroencephalogram and open field movement distance before and after stimulation.RESULTS(1)In the optical fiber recording experiment, Ca^(2+)signal was significantly decreased after intraperitoneal injection of Dex(40 μg·kg^(-1)) compared with before administration(P<0.01),but had no significant change in NS group(P>0.05).(2)The results of the photogenetic experiment showed that the δ wave proportion decreased significantly(P<0.001),the θ wave proportion had no significant change(P>0.05),the α wave proportion increased significantly(P<0.05),and the β wave proportion increased significantly(P<0.0001) when the basal forebrain neurons were stimulated by light.(3)After photogenetic activation, the exercise amount of mice in the open field was significantly increased(P<0.01).CONCLUSION Dexmedetomidine can inhibit the activity of γ-aminobutyric acid neurons in the basal forebrain of mice.Activation of basal forebrain γ-aminobutyric acidergic neurons decreased the depth of sedation in mice.

关 键 词：基底前脑γ-氨基丁酸能神经元 镇静 右美托咪定 

分 类 号：R965[医药卫生—药理学]