Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome
Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome
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DOI：
10.1136/gut.2003.018911
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发表时间：
2004-07-01
期刊：
影响因子：
24.5
通讯作者：
Fukudo, S
中科院分区：
文献类型：
--
作者：
Sagami, Y;Shimada, Y;Fukudo, S
背景与目的：促肾上腺皮质激素释放激素（CRH）是脑肠轴应激反应的主要介质。肠易激综合征（IBS）被认为是一种脑-肠连接紊乱，与对压力的过度反应有关。我们假设外周给药α -螺旋CRH (α -螺旋CRH)，一种非选择性CRH受体拮抗剂，可以改善肠易激综合征患者对肠道刺激的胃肠道运动、内脏感知和负面情绪。方法：选取10例正常人和10例符合Rome II标准的IBS患者作为研究对象。在基线、直肠电刺激（ES）期间和生理盐水治疗后恢复时测量降结肠张力和乙状结肠腔内压。结肠扩张或直肠ES后的内脏知觉在纵坐标尺度上作为阈值进行评估。在给予alphahCRH（10马克杯/千克）后重复同样的测量。结果：ES诱导IBS患者结肠运动指数明显高于对照组。在给予ahCRH后，IBS患者的这种反应被显著抑制，而对照组则没有。给药alphahCRH诱导控制组的气压袋体积显著增加，而IBS组则没有。alphahCRH显著降低IBS患者ES诱发的腹痛和焦虑的纵坐标量表。血浆促肾上腺皮质激素和血清皮质醇水平一般不受α - crh的抑制。结论：外周给药alphahCRH可改善肠易激综合征患者的胃肠运动、内脏感知和对肠道刺激的负性情绪，而不影响下丘脑-垂体-肾上腺轴。
Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients.Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 mug/kg).Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of ahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH.Conclusion: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.