肠易激综合征中5-羟色胺代谢异常

Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.

作者信息

Dunlop Simon P, Coleman Nicholas S, Blackshaw Elaine, Perkins Alan C, Singh Gulzar, Marsden Charles A, Spiller Robin C

机构信息

Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK.

出版信息

Clin Gastroenterol Hepatol. 2005 Apr;3(4):349-57. doi: 10.1016/s1542-3565(04)00726-8.

DOI:10.1016/s1542-3565(04)00726-8

PMID:15822040

Abstract

BACKGROUND & AIMS: 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover.

METHODS

Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers.

RESULTS

Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002).

CONCLUSIONS

C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.

摘要

背景与目的

5-羟色胺-3（5-HT 3）受体拮抗剂可改善腹泻型肠易激综合征（D-IBS）患者的症状，5-HT 4激动剂则有助于便秘型肠易激综合征（C-IBS）患者。这些数据分别提示D-IBS或C-IBS患者体内5-HT存在过量或不足。感染后肠易激综合征（PI-IBS）患者的含5-HT的肠嗜铬细胞（EC）数量增加。我们的目的是确定PI-IBS和C-IBS患者餐后5-HT的释放情况，并将其与黏膜5-HT周转率相关联。

方法

15例以腹泻为主的PI-IBS患者、15例C-IBS患者和15名健康对照者在进食标准520千卡餐后3小时内进行连续（少血小板）血浆5-HT测量。对直肠活检标本进行5-HT及其代谢产物5-羟吲哚乙酸（5-HIAA）检测。使用不透X线标志物测量结肠转运时间。

结果

与PI-IBS患者（26.7±4.5小时）和对照患者（34.1±4.5小时）相比，C-IBS患者的结肠转运时间延长（均值±标准误）（49.4±3.8小时）（P<.02）。与PI-IBS患者（5623±721毫摩尔/升·分钟）和对照患者（4822±598毫摩尔/升·分钟）相比，C-IBS患者餐后0至180分钟少血小板血浆5-HT曲线下面积（AUC）评估的5-HT释放显著降低（2593±309毫摩尔/升·分钟）（P<.001）。与C-IBS患者（31.2，范围15.2 - 40.5）纳克/升和对照患者（43.6，范围26.7 - 50.1）纳克/升相比，PI-IBS患者餐后血浆5-HT峰值显著更高（中位数，范围）（71.7，43.4 - 125.3）纳克/升（P<.01）。与对照患者1.12（范围0.17 - 3.1）相比，C-IBS和PI-IBS患者黏膜5-HIAA/5-HT比值评估的黏膜5-HT周转率均降低，分别为0.14（范围0.01 - 0.6）和0.21（范围0.02 - 2.5）（P<.002）。