酮替芬对腹泻型肠易激综合征患者胃肠道症状、内脏敏感性及肠道肥大细胞的影响

doi:10.12092/j.issn.1009-2501.2019.01.011

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (1): 63-70.doi: 10.12092/j.issn.1009-2501.2019.01.011

酮替芬对腹泻型肠易激综合征患者胃肠道症状、内脏敏感性及肠道肥大细胞的影响

汪静¹，周海斌²，顾伟刚³，王霞³，杨建锋³

¹杭州市老年病医院药剂科，杭州 310022，浙江； ²杭州市老年病医院消化内科，杭州 310022，浙江； ³浙江大学医学院附属杭州市第一人民医院消化内科，杭州 310006，浙江

收稿日期:2018-10-17 修回日期:2018-11-30 出版日期:2019-01-26 发布日期:2019-01-25
通讯作者: 杨建锋，男，博士，主任医师，主要从事功能性胃肠疾病临床研究。 Tel：0571-56006995 E-mail：yjf-1976@163.com
作者简介:汪静，女，本科，主管药师，主要从事消化系统药理机制研究。 Tel：15967152826 E-mail：wangjing5846@163.com
基金资助:
浙江省科技厅科技计划项目（2015C33251）

Effect of ketotifen on gastrointestinal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrheal

WANG Jing¹, ZHOU Haibin², GU Weigang³, WANG Xia³, YANG Jianfeng³

¹ Department of Pharmacy, Hangzhou Geriatric Hospital, Hangzhou 310022, Zhejiang, China; ²Department of Gastroenterology, Hangzhou Geriatric Hospital, Hangzhou 310022, Zhejiang, China; ³ Department of Gastroenterology, Hangzhou First People's Hospital Affiliated to School of Medicine of Zhejiang University, Hangzhou 310006, Zhejiang, China

Received:2018-10-17 Revised:2018-11-30 Online:2019-01-26 Published:2019-01-25

摘要/Abstract

摘要：

目的: 探讨酮替芬对腹泻型肠易激综合征（irritable bowel syndrome with diarrhea，IBS-D）患者胃肠道症状、内脏敏感性以及肠道肥大细胞的影响。方法: 纳入IBS-D患者按就诊顺序随机分为酮替芬组和安慰剂组，酮替芬组患者予酮替芬片1 mg，2次/d，口服，对照组给予安慰剂口服，疗程均为8周。两组患者分别在治疗前、治疗后8周进行胃肠道症状评估量表调查、肛门直肠感觉功能测定、肠道肥大细胞（mast cell，MC）数量和活性状态检测。结果:（1）共纳入IBS-D患者87例，酮替芬组44例，对照组43例，两组间在年龄、性别间差异无统计学意义（P>0.05）；（2）酮替芬组胃肠道症状改善总有效率明显高于对照组（72.7% vs. 34.9%，P<0.01）；（3）与治疗前相比，酮替芬组治疗后初始感觉、排便急迫感、不适/疼痛阈值均明显提高（P<0.05），而对照组治疗前后无明显变化（P>0.05）；（4）与治疗前相比，酮替芬组治疗后回肠末端MC数量减少，乙状结肠、升结肠、回肠末端MC脱颗粒状态比例均明显下降，差异有统计学意义（P<0.01）；而对照组治疗前后各部位MC数量及脱颗粒状态比例无明显变化（P>0.05）；（5）酮替芬组共发生不良反应5例，发生率为11.4%，主要表现为困倦感或乏力感，继续服药1周后消失。结论: 酮替芬能明显缓解IBS-D患者的胃肠道症状并改善内脏高敏感，这与它具有减少肠道黏膜尤其回肠末端MC数量并降低活性的作用密切相关。

关键词: 酮替芬, 腹泻型肠易激综合征, 内脏敏感性, 肥大细胞

Abstract:

AIM: To investigate the effects of ketotifen on abdominal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrhea (IBS-D). METHODS: Patients with IBS-D were randomly divided into ketotifen group and placebo group, the ketotifen group were oral administration of ketotifen tablets, 1 mg, bid for 8 weeks, the control group were received oral placebo for 8 weeks. Gastrointestinal symptoms evaluation scale questionnaire, anorectal sensory function, the number and activity status of mast cell (MC) were measured before and 8 weeks after treatment in these two group. RESULTS: (1) A total of 87 IBS-D patients were included, 44 in ketotifen group and 43 in control group, there was no significant difference in age and sex between the two groups. (2) Total effective rate of improvement of gastrointestinal symptoms in ketotifen group was significantly higher than that in control group (72.7% vs. 34.9%, P<0.01). (3) Compared with before treatment, first sensation, urge to defecation, discomfort/pain sensory thresholds of ketotifen group were significantly increased after treatment (P<0.05), no significant changes were observed in the control group (P>0.05); (4) Compared with before treatment, the number of MC in terminal ileum, the proportion of MC degranulation state in the terminal ileum, ascending colon, sigmoid colon in ketotifen group were significantly decreased after treatment (P<0.05), there was no significant change in the number of MC and the proportion of degranulation state in the control group (P>0.05); (5) 5 patients (11.4%) in ketotifen group went through adverse reactions, mainly manifested as feeling of drowsiness or fatigue, which disappeared after taking the drug one week. CONCLUSION: Ketotifen can significantly relieve the gastrointestinal symptoms and improve the visceral sensitivity of patients with IBS-D, which is closely related to its effect on reducing the number and activity of MC in intestinal mucosa, especially the terminal ileum.

Key words: ketotifen, irritable bowel syndrome with diarrheal, visceral sensitivity, mast cells

中图分类号:

R364.5
R574

汪静，周海斌，顾伟刚，王霞，杨建锋. 酮替芬对腹泻型肠易激综合征患者胃肠道症状、内脏敏感性及肠道肥大细胞的影响[J]. 中国临床药理学与治疗学, 2019, 24(1): 63-70.

WANG Jing, ZHOU Haibin, GU Weigang, WANG Xia, YANG Jianfeng. Effect of ketotifen on gastrointestinal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrheal[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 63-70.

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酮替芬对腹泻型肠易激综合征患者胃肠道症状、内脏敏感性及肠道肥大细胞的影响

Effect of ketotifen on gastrointestinal symptoms, visceral sensitivity and intestinal mast cells in patients with irritable bowel syndrome with diarrheal

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