Reed D E, Zhang Y, Beyak M J, Lourenssen S, Blennerhassett M G, Paterson W G, Vanner S J
GI Diseases Research Unit, Queen's University, Kingston, ON, Canada.
Neurogastroenterol Motil. 2016 Apr;28(4):569-80. doi: 10.1111/nmo.12755. Epub 2016 Jan 6.
A relationship between stress and the symptoms of irritable bowel syndrome (IBS) has been well established but the cellular mechanisms are poorly understood. Therefore, we investigated effects of stress and stress hormones on colonic descending inhibition and transit in mouse models and human tissues.
Stress was applied using water avoidance stress (WAS) in the animal model or mimicked using stress hormones, adrenaline (5 nM), and corticosterone (1 μM). Intracellular recordings were obtained from colonic circular smooth muscle cells in isolated smooth muscle/myenteric plexus preparations and the inhibitory junction potential (IJP) was elicited by nerve stimulation or balloon distension oral to the site of recording.
Water avoidance stress increased the number of fecal pellets compared to control (p < 0.05). WAS also caused a significant increase in IJP amplitude following balloon distension. Stress hormones also increased the IJP amplitude following nerve stimulation and balloon distension (p < 0.05) in control mice but had no effect in colons from stressed mice. No differences were observed with application of ATP between stress and control tissues, suggesting the actions of stress hormones were presynaptic. Stress hormones had a large effect in the nerve stimulated IJP in human colon (increased >50%). Immunohistochemical studies identified alpha and beta adrenergic receptor immunoreactivity on myenteric neurons in human colon.
CONCLUSIONS & INFERENCES: These studies suggest that WAS and stress hormones can signal via myenteric neurons to increase inhibitory neuromuscular transmission. This could lead to greater descending relaxation, decreased transit time, and subsequent diarrhea.
应激与肠易激综合征（IBS）症状之间的关系已得到充分证实，但细胞机制尚不清楚。因此，我们在小鼠模型和人体组织中研究了应激和应激激素对结肠下行抑制和转运的影响。
在动物模型中采用避水应激（WAS）施加应激，或使用应激激素肾上腺素（5 nM）和皮质酮（1 μM）模拟应激。在离体平滑肌/肌间神经丛制备物中从结肠环行平滑肌细胞进行细胞内记录，并通过神经刺激或在记录部位近端的球囊扩张引发抑制性接头电位（IJP）。
与对照组相比，避水应激增加了粪便颗粒数量（p < 0.05）。球囊扩张后，WAS还导致IJP幅度显著增加。应激激素在对照组小鼠中神经刺激和球囊扩张后也增加了IJP幅度（p < 0.05），但对应激小鼠的结肠无影响。应激组和对照组组织之间应用ATP后未观察到差异，表明应激激素的作用是突触前的。应激激素对人结肠神经刺激的IJP有很大影响（增加>50%）。免疫组织化学研究确定了人结肠肌间神经元上的α和β肾上腺素能受体免疫反应性。
这些研究表明，WAS和应激激素可通过肌间神经元发出信号，增加抑制性神经肌肉传递。这可能导致更大程度的下行松弛、转运时间缩短以及随后的腹泻。
