Dalziel J E, Young W, Bercik P, Spencer N J, Ryan L J, Dunstan K E, Lloyd-West C M, Gopal P K, Haggarty N W, Roy N C
Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.
Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
Neurogastroenterol Motil. 2016 Aug;28(8):1241-51. doi: 10.1111/nmo.12824. Epub 2016 Mar 29.
Dysmotility in the gastrointestinal (GI) tract often leads to impaired transit of luminal contents leading to symptoms of diarrhea or constipation. The aim of this research was to develop a technique using high resolution X-ray imaging to study pharmacologically induced aged rat models of chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation. The 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist prucalopride was used to accelerate transit, and the opioid agonist loperamide was used to delay transit.
Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or loperamide (in dimethyl sulfoxide, DMSO) for 7 days by continuous 7-day dosing. To determine the GI region-specific effect, transit of six metallic beads was tracked over 12 h using high resolution X-ray imaging. An established rating scale was used to classify GI bead location in vivo and the distance beads had propagated from the caecum was confirmed postmortem.
Loperamide (1 mg/kg) slowed stomach emptying and GI transit at 9 and 12 h. Prucalopride (4 mg/kg) did not significantly alter GI transit scores, but at a dose of 4 mg/kg beads had moved significantly more distal than the caecum in 12 h compared to controls.
CONCLUSIONS & INFERENCES: We report a novel high-resolution, non-invasive, X-ray imaging technique that provides new insights into GI transit rates in live rats. The results demonstrate that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit.
胃肠道动力障碍常导致肠腔内容物转运受损，进而引发腹泻或便秘症状。本研究的目的是开发一种利用高分辨率X射线成像技术来研究药物诱导的慢性胃肠道动力障碍老年大鼠模型的方法，该模型可模拟加速转运（腹泻）或便秘。使用5-羟色胺4型（5-HT4）受体激动剂普芦卡必利来加速转运，使用阿片类激动剂洛哌丁胺来延缓转运。
18个月大的雄性大鼠连续7天每天给予0、1、2或4mg/kg的普芦卡必利或洛哌丁胺（溶于二甲亚砜，DMSO）。为了确定胃肠道区域特异性效应，使用高分辨率X射线成像在12小时内追踪6颗金属珠的转运情况。使用既定的评分量表对体内胃肠道珠子的位置进行分类，并在死后确认珠子从盲肠传播的距离。
洛哌丁胺（1mg/kg）在9小时和12小时时减缓了胃排空和胃肠道转运。普芦卡必利（4mg/kg）并未显著改变胃肠道转运评分，但在4mg/kg的剂量下，与对照组相比，12小时内珠子移动到盲肠远端的距离明显更远。
我们报告了一种新型的高分辨率、非侵入性X射线成像技术，该技术为活体大鼠的胃肠道转运速率提供了新的见解。结果表明，洛哌丁胺减缓了老年大鼠的整体转运，而普芦卡必利增加了胃排空并加速了结肠转运。
