Brain orexin improves intestinal barrier function via the vagal cholinergic pathway
Brain orexin improves intestinal barrier function via the vagal cholinergic pathway
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脑食欲素通过迷走神经胆碱能途径改善肠道屏障功能
DOI：
10.1016/j.neulet.2019.134592
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发表时间：
2020
影响因子：
2.5
通讯作者：
Ohhira Masumi
中科院分区：
文献类型：
--
作者：
Okumura Toshikatsu;Nozu Tsukasa;Ishioh Masatomo;Igarashi Sho;Kumei Shima;Ohhira Masumi
食欲素是参与许多功能的神经肽。在胃肠道功能方面，食欲素具有中枢调节胃分泌、胃肠动力和内脏感觉的作用。然而，关于中枢食欲素在控制肠屏障功能中的作用知之甚少。本研究旨在阐明脑食欲素是否在控制肠通透性中发挥作用。通过定量大鼠结肠组织中吸收的伊文思蓝来估计体内结肠通透性。脑池内注射食欲素A（orexin-A）可剂量依赖性地阻断脂多糖（lipopolysaccharide，LPS）或促肾上腺皮质激素释放因子（corticotropin-releasing factor，CRF）引起的肠通透性增加，而腹腔注射食欲素A则不能阻断，阿托品或迷走神经切断可阻断中枢食欲素A的作用。静脉注射中枢迷走神经兴奋剂2-脱氧-D-葡萄糖（2-DG）可显著阻断LPS引起的肠通透性增加，阿托品可阻断2-DG的作用。脑池内注射SB-334687（一种选择性食欲素1受体拮抗剂）可显著阻断2-DG诱导的肠通透性增高的改善作用。这些结果表明，外源性施用或内源性释放的食欲素通过迷走胆碱能途径中枢性地改善LPS引起的肠通透性过高。研究结果还首次表明，大脑可以控制肠道通透性。神经肽通过改善肠道屏障功能对宿主的神经元快速保护优势可能有助于我们理解与肠道通透性改变相关的应激敏感性胃肠疾病如肠易激综合征的脑-肠相互作用。
Orexins are neuropeptides that are implicated in a number of functions. With regard to the gastrointestinal functions, orexin acts centrally to regulate gastric secretion, gastrointestinal motility and visceral sensation. Little is however known about a role of central orexin in the control of intestinal barrier function. The present study was performed to clarify whether brain orexin plays a role in the control of intestinal permeability. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternally administered orexin-A but not orexin-B dose-dependently blocked the increased intestinal permeability by lipopolysaccharide (LPS) or corticotropin-releasing factor while intraperitoneally injected orexin-A failed to block it. Atropine or vagotomy abolished the action by central orexin-A. Intravenous injection of 2-deoxy-D-glucose (2-DG), a central vagal stimulant, significantly blocked the LPS-induced increase in intestinal permeability and atropine prevented the action of 2-DG. Intracisternal injection of SB-334687, a selective orexin 1 receptor antagonist, significantly blocked the action of 2-DG-induced improvement of intestinal hyperpermeability. These results suggest that exogenously administered or endogenously released orexin acts centrally to improve the intestinal hyperpermeability by LPS via the vagal cholinergic pathway. The findings also suggest for the first time that the brain could control intestinal permeability. The neuronal rapid protective advantage to the host by improving the intestinal barrier function by the neuropeptide may help us understand the brain-gut interaction in stress sensitive gastrointestinal disorders like irritable bowel syndrome associated with the altered intestinal permeability.