Division of Gastroenterology, Department of Pediatrics, Centre Hospitalier Universitaire Ste-Justine, Montréal, Quebec, Canada.
Gastroenterology. 2010 Jul;139(1):249-58. doi: 10.1053/j.gastro.2010.03.032. Epub 2010 Mar 17.
BACKGROUND & AIMS: In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signaling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms.
Ninety-eight children undergoing gastroscopy or colonoscopy were studied prospectively. Biopsy specimens were evaluated for inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) were assessed by quantitative real-time reverse-transcription polymerase chain reaction.
Data from 12 children with IBS and 17 with FD were compared with age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and with subjects with organic disorders. In patients with FD, a small number of immune cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect to the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ cells in the lamina propria although all patients showed at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content (P < .01) and lower SERT mRNA (P < .05) were detected as compared with controls. Severe inflammation in the colonic mucosa had a high impact on 5-HT signaling with a significant decrease in enterochromaffin cells (P < .01) and 5-HT content (P < .01) and a high SERT mRNA expression (P < .01).
These results confirm the role of 5-HT signaling in IBS in children and argue against such a role in FD.
在成年人中,肠易激综合征(IBS)和功能性消化不良(FD)是常见的慢性疾病,通常在儿童时期开始。我们研究了儿童的肠黏膜 5-羟色胺(5-HT)信号转导,因为我们认为具有较短病史的受试者的数据可能会增进我们对潜在病理生理机制的理解。
前瞻性地研究了 98 例接受胃镜或结肠镜检查的儿童。通过定量实时逆转录聚合酶链反应评估活检标本的炎症、肠嗜铬细胞数量、5-HT 含量以及合成酶色氨酸羟化酶 1 和 5-HT 转运体(SERT)的信使 RNA(mRNA)水平。
将 12 例 IBS 患儿和 17 例 FD 患儿的数据与年龄匹配的对照组(直肠活检 12 例,胃活检 12 例)和有器质性疾病的患儿进行了比较。在 FD 患儿中,半数患儿胃黏膜中观察到少量免疫细胞,但未发现 5-HT 途径异常。在 IBS 患儿中,与对照组相比,上皮内淋巴细胞和固有层 CD3+细胞无差异,但所有患儿均显示至少轻度炎症浸润。在 IBS 样本中,与对照组相比,5-HT 含量较高(P<0.01),SERT mRNA 较低(P<0.05)。结肠黏膜严重炎症对 5-HT 信号转导有很大影响,肠嗜铬细胞明显减少(P<0.01),5-HT 含量降低(P<0.01),SERT mRNA 表达升高(P<0.01)。
这些结果证实了 5-HT 信号转导在儿童 IBS 中的作用,但不能支持 FD 中存在这种作用。