Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
Department of Gastroenterology and Hepatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Am J Physiol Gastrointest Liver Physiol. 2024 May 1;326(5):G622-G630. doi: 10.1152/ajpgi.00298.2023. Epub 2024 Feb 20.
Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo. In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.
生物心理社会因素与肠道-脑相互作用障碍（DGBI）有关，并加重胃肠道症状。应激的病理生理改变的机制尚不清楚。促肾上腺皮质激素释放激素（CRH）是激素应激反应的中枢调节剂，对不同的器官系统有不同的影响。本研究旨在探讨外周 CRH 输注对健康志愿者（HV）进食相关胃肠道症状、胃电活动和胃感觉运动功能的影响。在一项随机、双盲、安慰剂对照、交叉研究中，我们评估了 CRH 对胃动力和敏感性的影响。将 HV 随机分为接受外周给予 CRH（100 µg 弹丸+1 µg/kg/h）或安慰剂（生理盐水），然后至少经过 7 天的洗脱期并分配到相反的治疗组。试验包括唾液样本、胃排空（GE）测试、体表面积胃映射（BSGM，胃测压计；Alimetry），以评估胃肌电活动和实时症状分析，以及胃顺应性研究，以评估胃对扩张和顺应性的敏感性。20 名 HV [13 名女性，平均年龄 29.2±5.3 岁，体重指数（BMI）23.3±3.8kg/m]完成了 GE 测试，其中 18 名 HV 还在 GE 测试期间进行了 BSGM 测量。CRH 暴露后 GE 半时间明显缩短（65.2±17.4 比 78.8±24.5 分钟， = 0.02），胃振幅显著增加[49.7（34.7-55.6）比 31.7（25.7-51.0）µV， < 0.01]，唾液皮质醇水平和餐后症状严重程度也增加。另外 11 名 HV 还在另一天进行了胃顺应性研究。然而，在等压扩张过程中不适的阈值、胃顺应性和适应性在 CRH 和安慰剂之间没有差异。在健康志愿者中，外周促肾上腺皮质激素释放激素（CRH）输注可加速胃排空率并增加餐后胃反应，同时症状加重，但不改变胃敏感性或餐后适应性。这些发现强调了应激和消化不良症状之间的重要联系，CRH 在介导这些作用中起着关键作用。
