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γ-氨基丁酸对大鼠摄食变化的影响及机制研究

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

摘要目的 探讨γ-氨基丁酸(γ-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4h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4h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 μA电刺激组、50 μA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4h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±8.4)%,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].大鼠NAc内微量注射GABA可明显增加4h累积摄食量[(155.72±18.84) kcal,t=3.41,P<0.05],该效应可被部分BIC拮抗[123.43±15.11)kcal,t=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,t=2.33,P<0.05].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.

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abstractsObjective To investigate whether γ-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 Zl 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 μA electrical stimulation group,50 μA 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:(78.8±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 for 4 h ((155.72± 18.84) kcal,t=3.41,P<0.05),which was antagonized by partial BIC (123.43± 15.11) kcal,t =3.28,P< 0.05).Electrical stimulation of ZI significantly increased the food intake in rats ((39.07± 11.27) kcal,t =2.96,P<0.05),and this effect can be partially antagonized by BIC ((34.17 ± 10.85) kcal,t =2.33,P< 0.05).Conclusion The ZI-NAc neural pathway regulates the discharge activity of rat gastric distension (GD)-sensitive neurons and the feeding status of rats,and the GABA receptor signaling pathway may be involved in mediating the process.

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