十氨基丁酸对大鼠摄食变化的影响及机制研究  

Effects of y-aminobutyric acid on feeding changes in rats and its potential mechanism

作　　者：王茜[1] 冷慧 栾晓[1] 郭菲菲[1] 孙向荣[1] 高胜利[1] 徐珞[1] Wang Qian;Leng Hui;Luan Xiao;Guo Feifei;Sun Xiangrong;Gao Shengli;Xu Luo(Department of Pathophysiology,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院病理学与病理生理学教研室,266021

出　　处：《中华行为医学与脑科学杂志》2019年第11期971-977,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目(81470815,81270460,81500414);中国博士后科学基金项目(2018M632627);山东省优秀中青年科学家科研奖励基金资助项目(BS2014YY009)。

摘　　要：目的探讨丫-氨基丁酸(丫-aminobutyric acid,GABA)受体信号通路是否参与调控丘脑未定带(thalamic undefined,ZI)-伏隔核(nucleus accumbens,NAc)神经通路对大鼠胃牵张(gastric distraction,GD)敏感神经元放电活动及对大鼠4 h累计摄食量的影响。方法随机选取6只大鼠,采用荧光金(fluorescent gold.FG)逆行追踪方法进行大鼠丘脑ZI与NAc之间的神经通路的观察;随机选取82只大鼠,分别进行大鼠胃部置球囊术,NAc核团置微电极,ZI核团置刺激电极,采用单细胞放电记录方法观察电刺激ZI对大鼠NAc内GD敏感神经元兴奋性的影响;随机选取18只大鼠,按照随机数字表发分为三组,每组6只,分别为NS组、GABA组、GABA+GABA受体拮抗剂荷包牡丹碱(BIC)组,采用大鼠NAc核团埋置套管并注入GABA及BIC的方法,观察大鼠4 h累计摄食量变化;随机选取18只大鼠,按照随机数字表发分为三组,每组6只,分别为假刺激(SS)组、50 jxA电刺激组、50“A电刺激+BIC组,采用电刺激大鼠ZI及大鼠NAc注射BIC的方法,观察大鼠4 h累计摄食量变化。结果FG逆行追踪结合荧光免疫组织化学染色结果显示,在ZI可见有GABA和FG双重标记的神经元。电刺激ZI,大鼠NAc中GABA敏感性GD神经元放电频率显著增多[GD-E增幅:(78.8士&4)%,GD-I增幅:(89.3±9.2)%,P<0.01],但该效应可被BIC拮抗[GD-E增幅:(113.8±13.6)%,GD-I增幅:(121.8±14.2)%,P<0.01]o大鼠NAc内微量注射GABA可明显增加4 h累积摄食量[(155.72±18.84)kcal,￠=3.41,P<0.05],该效应可被部分BIC拮抗[123.43±15,11)kcal,<=3.28,P<0.05]。电刺激大鼠ZI,大鼠摄食量明显增加[(39.07±11.27)kcal,t=2.96,P<0.05],该效应可被部分BIC拮抗[(34.17±10.85)kcal,Z=2.33,P<0.05]o结论ZI-NAc神经通路可调控鼠胃牵张(GD)敏感神经元放电活动及大鼠摄食情况,并且GABA-A受体信号通路可能参与该过程的调控。Objective To investigate whether-y-aminobutyric acid(GABA)receptor signaling pathway is involved in the regulation of thalamic undefined(ZI)-nucleus accumbens(NAc)neural pathways on gastric distraction(GD)-sensitive neuronal firing activity and the impact on food intake,the number of times and the frequency in rats.Methods Six rats were randomly selected and the neural pathway between ZI and NAc in rat thalamus was observed by fluorescent gold(FG)retrograde tracing method.Eighty-two rats were randomly selected,and the gastric balloon was placed in gastric cavity,the microelectrode was placed in the NAc,and the stimulating electrode was placed in the ZI.The single-cell discharge recording method was used to observe the effect of electrical stimulation ZI on the excitability of GD-sensitive neurons in rat NAc.Eighteen rats were randomly selected and were divided into three groups according to the random number table.They were NS group,GABA group,GABA+GABA receptor antagonist bicuculline(BIC)group with 6 in each group,and the rat NAc was used to embed the cannula.The method of GABA and BIC was injected to observe the changes of cumulative food intake in rats for 4 h.Eighteen rats were randomly selected and randomly divided into three groups:sham stimulation(SS)group,50 jxA electrical stimulation group,50|xA electrical stimulation+BIC group with 6 in each group.The 4 h cumulative food intake of rats was observed by electro-stimulation of rat ZI and rat NAc injection of BIC.Results Fluorescent gold retrograde tracking combined with fluorescent immunohistochemical staining showed that there were visible GABA and fluorescent gold double labeled neurons in ZI.Electrical stimulation of ZI,the frequency of GABA-sensitive GD neurons in rat NAc increased significantly(GD-E increase:(7&8±8.4)%,GD-I increase:(89.3±9.2)%,P<0.01),but the inhibitory effect was antagonized by BIC(GD-E increase:(113.8±13.6)%,GD-I increase:(121.8±14.2)%,P<0.01).Microinjection of GABA in rat NAc significantly increased the cumulative food intake

关 键 词：未定带 伏隔核 卄氨基丁酸 胃牵张敏感神经元 摄食 

分 类 号：R28[医药卫生—中药学]