Orexin-A通路对胃运动的调控研究

目的:探讨下丘脑外侧核(LHA)-伏隔核(NAcc)orexin-A神经和功能通路构成及该通路对胃运动的影响及潜在机制。方法:将健康成年雄性Wistar大鼠随机分为逆行追踪组和胃运动组:逆行追踪组大鼠采用逆行追踪技术结合免疫荧光组织化学染色法,观察下丘脑外侧核-伏隔核间是否存在orexin-A神经通路;胃运动组大鼠通过在体胃运动研究,观察伏隔核内微量注射不同浓度orexin-A对大鼠胃运动幅度和频率的影响,以及电刺激下丘脑外侧核后,大鼠胃运动的变化及机制。结果:荧光逆行追踪结合荧光免疫组织化学染色结果显示:下丘脑外侧核内有荧光金和orexin-A双重标记的神经元。胃运动研究结果显示:伏隔核内微量注射orexin-A,大鼠胃运动幅度和频率显著增加,并呈现显著剂量依赖关系(P0.05),伏隔核预先微量注射SB-334867,可反转该效应(P0.05)。电刺激下丘脑外侧核,大鼠胃运动幅度和频率显著增强(P0.05)。同样,伏隔核内微量注射SB-334867,再电刺激下丘脑外侧核,电刺激导致的胃运动增强效应显著减弱(P0.05)。结论:下丘脑外侧核-伏隔核存在orexin-A神经和功能通路,该通路可能通过orexin-A受体介导参与胃动力和能量代谢调控。

Effect of Orexin-A Pathway on the Gastric Motility in Rats

ABSTRACT Objective: To explore the effects and the potential regulation mechanisms of orexin-A and the neural pathways between lateral nucleus (LHA) and nucleus accumbens (NAcc) on gastric motility. Methods: Adult male wiatar rats were used, and randomly divided into two parts. We used retrograde tracing and fluorescent -immunohistochemistry staining method to observe the neural pathways between lateral nucleus (LHA) and nucleus accumbens (NAcc) in the first part of rats. We used gastric motility recording in vivo to observe the change of the amplitude and frequency of gastric constriction following by nucleus accumbens micinject differents levels of orexin-A, and the change of gastric motility after electrical stimulated lateral nucleus in the two part of rats. Results: Retrograde tracing and fluorescent immunohistochemistry study shown that orexin-A/ fluorogold (FG) dual labelled neurons were found in the lateral nucleus. Gastric motility study illustrated that orexin-A microinject to the nucleus accumbens, the amplitude and frequency of gastric motility in rats were dose-dependently increased significantly(P < 0.05). SB-334867 microinject to the nucleus accumbens could block the effect on gastric contraction (P < 0.05). The amplitude and frequency of gastric motility were significantly enhanced after electrical stimulation of LHA in rats(P < 0.05). The effect on gastric motility included by orexin-A was disappeared or weaken following by SB-334867 microinject to the nucleus accumbens(P < 0.05). Conclusion: There exist the neural pathways between lateral nucleus and nucleus accumbens, it can regulate the gastric motility, and this way maybe mediated by the orexin-A receptor signaling pathway.