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普芦卡必利对豚鼠术后肠麻痹的影响。

The effects of prucalopride on postoperative ileus in guinea pigs.

机构信息

Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Korea.

出版信息

Yonsei Med J. 2013 Jul;54(4):845-53. doi: 10.3349/ymj.2013.54.4.845.

Abstract

PURPOSE

Postoperative ileus (POI) is an impairment of coordinated gastrointestinal (GI) motility that develops as a consequence of abdominal surgery and is a major factor contributing to patient morbidity and prolonged hospitalization. The aim of this study was to investigate the effects of different 5-hydroxytryptamine 4 (5-HT₄) receptor agonists, which stimulate excitatory pathways, on a POI model.

MATERIALS AND METHODS

The experimental model of POI in guinea pigs was created by laparotomy, gentle manipulation of the cecum for 60 seconds, and closure by suture, all under anesthesia. Different degrees of restoration of GI transit were measured by the migration of charcoal. Colonic transit was indirectly assessed via measurement of fecal pellet output every hour for 5 hours after administration of various doses of mosapride, tegaserod, prucalopride, and 5-HT.

RESULTS

Charcoal transit assay showed that various 5-HT₄ receptor agonists can accelerate delayed upper GI transit in a dose-dependent manner. However, fecal pellet output assay suggested that only prucalopride had a significant effect in accelerating colonic motility in POI.

CONCLUSION

Although mosapride, tegaserod, and prucalopride produce beneficial effects to hasten upper GI transit in the POI model, prucalopride administered orally restores lower GI transit as well as upper GI transit after operation in a conscious guinea pig. This drug may serve as a useful candidate for examination in a clinical trial for POI.

摘要

目的

术后肠麻痹(POI)是一种胃肠道(GI)协调运动障碍,是腹部手术后的主要并发症之一,会导致患者发病率增加和住院时间延长。本研究旨在探讨不同的 5-羟色胺 4(5-HT₄)受体激动剂(刺激兴奋途径)对 POI 模型的影响。

材料和方法

通过剖腹手术、轻柔操作盲肠 60 秒和缝合关闭,在麻醉下建立豚鼠 POI 实验模型。通过炭粒迁移来测量不同程度的 GI 转运恢复情况。通过测量给药后 5 小时内每小时的粪便颗粒排出量,间接评估结肠转运。

结果

炭粒转运试验表明,各种 5-HT₄受体激动剂可以剂量依赖性地加速延迟的上 GI 转运。然而,粪便颗粒排出试验表明,只有普芦卡必利能显著加速 POI 中的结肠蠕动。

结论

虽然莫沙必利、替加色罗和普芦卡必利对上 GI 转运有促进作用,但在清醒豚鼠中,口服普芦卡必利可以恢复下 GI 转运和术后上 GI 转运。这种药物可能是 POI 临床试验的一个有用候选药物。

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