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目的:探讨ARC orexin-A对胃传入信息以及胃运动的调控及机制。方法:采用细胞外放电记录方法,鉴定ARC orexin胃牵张敏感神经元(Gastric distention sensitive neurons,GD),并探讨ARC内orexin-A对GD神经元放电活动的影响及机制;采用ARC微量注射orexin-A和及其受体阻断剂SB334867,观察大鼠胃收缩幅度和频率的改变。结果:大鼠ARC共记录到149个GD神经元,其中GD-E神经元91个,GD-I神经元58个。ARC微量注射orexin-A,62个(62/91,68.1%)GD-E神经元兴奋性显著增加,其放电频率由4.27±0.58 Hz增加到8.46±0.95 Hz(P<0.01);39个(39/58,67.2%)GD-I神经元兴奋性也显著增强,其放电频率由4.02±0.53 Hz增加到5.43±0.57 Hz(P<0.05)。然而,ARC给予大鼠orexin-A受体拮抗剂SB334867,再给予orexin-A,orexin-A兴奋效应完全被阻断(P>0.05)。胃运动实验结果显示:在ARC注射不同浓度orexin-A,大约5 min后,大鼠胃收缩幅度和频率呈剂量依赖性增加(P<0.05~0.01)。ARC注射SB334867,可完全消除orexin-A对大鼠胃运动的兴奋效应(P<0.05)。结论:ARC orexin-A对大鼠GD神经元和胃运动有调控作用,该作用可能通过调控Orexin A受体活动实现的。
Objective: To investigate the regulation and mechanism of ARC orexin-A on gastric afferent information and gastric motility. Methods: The extracellular discharge recording method was used to identify the ARC orexin gastric distraction sensitive neurons (GD) and to explore the effect and mechanism of orexin-A on the discharge activity of GD neurons in ARC. The microinjection of orexin -A and its receptor blocker SB334867 to observe the change of rat gastric contraction amplitude and frequency. Results: A total of 149 GD neurons were recorded in ARC of rats, including 91 GD-E neurons and 58 GD-I neurons. The excitability of GD-E neurons in 62 (62/91, 68.1%) neurons was significantly increased by ARC microinjection of orexin-A, and the discharge frequency increased from 4.27 ± 0.58 Hz to 8.46 ± 0.95 Hz (P <0.01) 39/58, 67.2%) GD-I neurons were also significantly increased in excitability. The discharge frequency increased from 4.02 ± 0.53 Hz to 5.43 ± 0.57 Hz (P <0.05). However, ARC administration of orexin-A receptor antagonist SB334867 in rats, and then given orexin-A, orexin-A excitatory effect was completely blocked (P> 0.05). The result of gastric motility test showed that after ARC injection of different concentrations of orexin-A, the amplitude and frequency of gastric contraction increased in a dose-dependent manner (P <0.05 ~ 0.01) after about 5 min. ARC injection of SB334867 completely abolished the excitatory effect of orexin-A on rat gastric motility (P <0.05). CONCLUSION: ARC orexin-A regulates GD neurons and gastric motility in rats, which may be mediated through the regulation of Orexin A receptor activity.