LHA-VTA Orexin-A通路对大鼠胃牵张敏感神经元放电活动和胃功能的调控研究

Regulation of LHA-VTA Orexin-A Pathway on Discharge Activity of Gastric Distension Responsive Neurons and Gastric Emptying in Rats/

目的:观察下丘脑外侧核(LHA)-中脑腹侧被盖区(VTA)Orexin-A通路对大鼠胃牵张敏感神经元放电活动和胃排空的影响。方法:大鼠经VTA给予Orexin-A,采用单细胞外放电记录方法,观察VTA内胃牵张敏感神经元放电活动;酚红定量法测定大鼠胃排空,并观察电刺激下丘脑外侧核后,VTA内Orexin-A反应性胃牵张敏感神经元放电活动及大鼠胃排空的变化。结果:电生理记录到58个胃牵张敏感VTA神经元(GD),胃扩张后呈现兴奋效应(GD-E)41个,呈现抑制效应(GD-I)17个。VTA微量注射Orexin-A,41个GD-E中,68.29%的神经元放电频率显著升高(P<0.05),而17个GD-I中,70.59%的神经元放电频率显著增加(P<0.05)。VTA预先注射Orexin1型受体拮抗剂SB-334867,则Orexin-A对胃牵张敏感神经元的作用被完全阻断(P>0.05)。电刺激LHA,在VTA记录到31个Orexin-A反应性GD-E神经元,其中有70.97%神经元进一步呈现兴奋效应(P<0.05);在VTA记录到的17个Orexin-A反应性GD-I神经元,其中有64.71%神经元放电频率显著升高(P<0.05)。SB-334867预处理VTA可抑制电刺激LHA的作用(P<0.05)。胃排空研究结果显示,VTA内微量注射Orexin-A和电刺激LHA,大鼠胃排空均显著增加(P<0.05),VTA预先微量注射SB-334867,可阻断该效应(P<0.05)。结论:下丘脑LHA-VTA存在Orexin-A功能通路,该通路可能参与胃功能的调控。

Objective:To observe the effect of Orexin-A pathway from lateral hypothalamic nucleus(LHA)to ventral tegmental area(VTA)on the discharge activity of gastric distension(GD)responsive neurons and gastric emptying in rats.Method:Extracellular discharges of single unit neuron was used to observe the discharge activity of GD-responsive neurons in VTA.Phenol red quantitative method was used to measure the gastric emptying in rats.The changes of the discharge activity of GD-responsive neurons in VTA and the gastric emptying in rats were observed after VTA Orexin-A administration or LHA electrical stimulation.Result:Electrophysiological study showed that 58 GD were recorded in the VTA,of which 41 showed excitatory effects(GD-E)and 17 showed inhibitory effects(GD-I).Out of the 41 GD-E neurons,the discharge frequency of 68.29%was significantly increased(P<0.05).Out of GD-I neurons,the discharge frequency of 70.59%was significantly rised(P<0.05).After preadministration of Orexin-A receptor antagonist SB334867 into VTA,the effect of Orexin-A on GD sensitive neurons was completely blocked(P>0.05).31 Orexin-A reactive GD-E neurons in VTA were recorded after electrical stimulation of LHA,of which 70.97%neurons showed further excitatory effects(P<0.05);in orexin-A sensitive GD-I neurons,the discharge frequency of 64.71%neurons were significantly rised(P<0.05).Orexin-A receptor antagonist SB-334867 could inhibit the effects(P<0.05).The gastric emptying of rats was significantly increased by microinjection of Orexin-A in VTA(P<0.05)or electrical stimulation of LHA(P<0.05).Pre-microinjection of SB-334867 into VTA could block the effects(P<0.05).Conclusion:There is an Orexin-A pathway between LHA-VTA,which may be involved in the regulation of gastric function.