Department of Anatomy, Sapporo Medical University School of Medicine, Japan.
Am J Physiol Gastrointest Liver Physiol. 2012 Aug 15;303(4):G519-28. doi: 10.1152/ajpgi.00390.2011. Epub 2012 May 31.
Because of the difficulties in developing suitable animal models, the pathogenesis of stress-induced functional gastrointestinal disorders is not well known. Here we applied the communication box technique to induce psychological stress in rats and then examined their gastrointestinal motility. We measured upper and lower gastrointestinal motility induced by acute and chronic psychological stress and examined the mRNA expression of various neuropeptides in the hypothalamus. Chronic psychological stress disrupted the fasted motility in the antrum and accelerated motility in the proximal colon. mRNA expression of AVP, oxytocin, and urocortin 3 was increased by chronic psychological stress. Intracerebroventricular (ICV) injection of urocortin 3 disrupted the fasted motility in the antrum, while ICV injection of Ucn3 antiserum prevented alteration in antral motility induced by chronic psychological stress. ICV injection of AVP accelerated colonic motility, while ICV injection of SSR 149415, a selective AVP V1b receptor antagonist, prevented alteration in proximal colonic motility induced by chronic psychological stress. Oxytocin and its receptor antagonist L 371257 had no effect on colonic motility in either the normal or chronic psychological stress model. These results suggest that chronic psychological stress induced by the communication box technique might disrupt fasted motility in the antrum via urocortin 3 pathways and accelerates proximal colonic motility via the AVP V1b receptor in the brain.
由于难以开发出合适的动物模型,应激诱导的功能性胃肠疾病的发病机制还不清楚。在这里,我们应用交流盒技术诱导大鼠产生心理应激,然后检查它们的胃肠动力。我们测量了急性和慢性心理应激诱导的上消化道和下消化道运动,并检查了下丘脑各种神经肽的 mRNA 表达。慢性心理应激破坏了空腹时胃窦的运动,加速了近端结肠的运动。AVP、催产素和 Ucn3 的 mRNA 表达被慢性心理应激所增加。脑室内(ICV)注射 Ucn3 抗血清破坏了胃窦的空腹运动,而 Ucn3 抗血清防止了慢性心理应激引起的胃窦运动改变。AVP 加速了结肠的运动,而选择性 AVP V1b 受体拮抗剂 SSR149415 则防止了慢性心理应激引起的近端结肠运动改变。催产素及其受体拮抗剂 L371257 对正常或慢性心理应激模型中的结肠运动均无影响。这些结果表明,交流盒技术诱导的慢性心理应激可能通过 Ucn3 途径破坏胃窦的空腹运动,通过大脑中的 AVP V1b 受体加速近端结肠的运动。