Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Frontier Research Institute for Interdisciplinary Sciences, Tohoku University Graduate School of Medicine, Sendai, Japan.
PLoS One. 2018 Jul 6;13(7):e0199698. doi: 10.1371/journal.pone.0199698. eCollection 2018.
Corticotropin-releasing hormone (CRH) mediates stress responses in the brain-gut axis. Administration of CRH modulates brain activation, for example by controlling the autonomic nervous system in response to colorectal distention. Here, we investigated the relationship between sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to colorectal distention in patients with irritable bowel syndrome (IBS). We enrolled 32 patients with IBS (16 women and 16 men) and 32 healthy subjects (16 women and 16 men), and randomly divided them between CRH and saline injection groups. The patients randomly underwent no (0 mmHg), mild (20 mmHg), or strong (40 mmHg) colorectal distension. CRH (2 μg/kg) or saline was then administered via injection, and the distention protocol was repeated. The heart rate (HR) and HR variability (HRV; calculated as the low [LF] to high frequency [HF] peak ratio, LF/HF) were analyzed using electrocardiography. Plasma noradrenaline, adrenaline, adrenocorticotropic hormone (ACTH), and cortisol levels were measured at the time of each distention. Plasma adrenaline levels were shown to be associated with plasma ACTH levels in HCs injected with CRH during distention using structural equation modeling analysis. Patients with IBS injected with placebo during distention displayed a closer association between these two parameters than those injected with CRH. Generalized estimating equation analysis revealed a significant distention × group × drug interaction for HF power. Moreover, there was a strong correlation between adrenaline and HRV upon CRH injection in controls, but not patients with IBS. The relationship between HPA-sympathoadrenal responses and CRH levels during colorectal distention differs between patients with IBS and controls. Modulation of adrenal gland activity in response to ACTH stimulation may contribute to the brain-gut pathophysiology characteristic of IBS.
促肾上腺皮质激素释放激素（CRH）介导脑-肠轴的应激反应。CRH 的给药调节大脑激活，例如通过控制自主神经系统对结直肠扩张的反应。在这里，我们研究了肠易激综合征（IBS）患者结直肠扩张时交感肾上腺和下丘脑-垂体-肾上腺（HPA）反应之间的关系。我们招募了 32 名 IBS 患者（16 名女性和 16 名男性）和 32 名健康受试者（16 名女性和 16 名男性），并将他们随机分为 CRH 和盐水注射组。患者随机接受无（0mmHg）、轻度（20mmHg）或强烈（40mmHg）结直肠扩张。然后通过注射给予 CRH（2μg/kg）或生理盐水，并重复扩张方案。使用心电图分析心率（HR）和心率变异性（HRV；计算为低频[LF]到高频[HF]峰值比，LF/HF）。在每次扩张时测量血浆去甲肾上腺素、肾上腺素、促肾上腺皮质激素（ACTH）和皮质醇水平。结构方程模型分析显示，在使用 CRH 扩张期间，HC 中肾上腺素水平与血浆 ACTH 水平相关。与接受 CRH 注射的患者相比，接受安慰剂扩张的 IBS 患者这两个参数之间的相关性更密切。广义估计方程分析显示 HF 功率存在显著的扩张×组×药物相互作用。此外，在对照者中，CRH 注射后肾上腺素与 HRV 之间存在很强的相关性，但在 IBS 患者中没有。IBS 患者与对照组之间，结直肠扩张期间 HPA-交感肾上腺反应与 CRH 水平的关系不同。对 ACTH 刺激的肾上腺活动的调节可能有助于 IBS 的脑-肠病理生理学特征。
