Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome.
Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome.
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DOI：
10.1038/s41598-017-09635-x
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发表时间：
2017-09-29
影响因子：
4.6
通讯作者：
Fukudo S
中科院分区：
文献类型：
--
作者：
Kano M;Muratsubaki T;Van Oudenhove L;Morishita J;Yoshizawa M;Kohno K;Yagihashi M;Tanaka Y;Mugikura S;Dupont P;Ly HG;Takase K;Kanazawa M;Fukudo S
应激是肠易激综合征（IBS）的已知触发因素，并加剧其胃肠道症状。然而，潜在的生理机制仍然未知。在这里，我们调查下丘脑-垂体-肾上腺（HPA）轴，结肠动力，和自主反应促肾上腺皮质激素释放激素（CRH）管理以及脑活动的变化在IBS。该研究包括28名IBS患者和34名年龄和性别匹配的健康对照组。IBS患者表现出更大的促肾上腺皮质激素（ACTH）反应CRH比对照组。CRH后，男性IBS患者的结肠动力比男性HC患者增加更多。女性IBS患者表现出改变交感迷走神经平衡和较低的基础副交感神经张力相对于女性对照组。使用功能性磁共振成像测量了相同受试者对直肠扩张的脑反应，并测试了其与CRH个体ACTH反应的相关性。ACTH对CRH的反应与直肠扩张时膝前扣带皮层（pACC）的活性之间存在负相关，在对照组中发现，但在IBS患者中没有发现。从膝前ACC到HPA轴的自上而下的抑制性输入受损可能导致对CRH的神经内分泌和胃肠道反应改变。中枢作用的治疗可能会抑制应激诱导的IBS身体症状。
Stress is a known trigger of irritable bowel syndrome (IBS) and exacerbates its gastrointestinal symptoms. However, underlying the physiological mechanism remains unknown. Here, we investigated hypothalamic–pituitary–adrenal (HPA) axis, colonic motility, and autonomic responses to corticotropin-releasing hormone (CRH) administration as well as brain activity alterations in IBS. The study included 28 IBS patients and 34 age and sex-matched healthy control subjects. IBS patients demonstrated greater adrenocorticotropic hormone (ACTH) responses to CRH than control subjects. Male IBS patients had greater increases in colonic motility than male HCs after CRH. Female IBS patients showed altered sympathovagal balance and lower basal parasympathetic tone relative to female control subjects. Brain responses to rectal distention were measured in the same subjects using functional magnetic resonance imaging, and their associations with individual ACTH responses to CRH were tested. A negative association between ACTH response to CRH and activity in the pregenual anterior cingulate cortex (pACC) during rectal distention was identified in controls but not in IBS patients. Impaired top-down inhibitory input from the pregenual ACC to the HPA axis may lead to altered neuroendocrine and gastrointestinal responses to CRH. Centrally acting treatments may dampen the stress induced physical symptoms in IBS.
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