Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2016; 22(9): 2799-2810
Published online Mar 7, 2016. doi: 10.3748/wjg.v22.i9.2799
Development of a novel mouse constipation model
Chao Liang, Kai-Yue Wang, Zhi Yu, Bin Xu
Chao Liang, Kai-Yue Wang, Zhi Yu, Bin Xu, Key Laboratory of Integrated Acupuncture and Drugs Affiliated to the Ministry of Education of China, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Author contributions: Liang C designed and performed the experiments and wrote the paper; Wang KY performed the research; Yu Z and Xu B supervised the study and revised the paper; Liang C and Wang KY contributed equally to this work.
Supported by The National Key Basic Research Program 973 Program, No. 2011CB505206; the National Natural Science Foundation of China, No. 81202744 and No. 81373749.
Institutional review board statement: This study was reviewed and approved by Institutional Review Board of the Nanjing University of Chinese Medicine, Nanjing, China.
Institutional animal care and use committee statement: All experimental manipulations were undertaken in accordance with the principles of Laboratory Animal Care and the Guide for the Care and Use of Laboratory Animals, published by the National Science Council, China; and the study was approved by the Institutional Animal Care and Use Committee of Nanjing University of Chinese Medicine.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Bin Xu, PhD, Professor, Key Laboratory of Integrated Acupuncture and Drugs Affiliated to the Ministry of Education of China, Nanjing University of Chinese Medicine, No.138 Xianlin Road, Nanjing 210023, Jiangsu Province, China.
Telephone: +86-25-86798095 Fax: +86-25-86798095
Received: September 16, 2015
Peer-review started: September 20, 2015
First decision: October 14, 2015
Revised: October 28, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: March 7, 2016

AIM: To establish a novel mouse constipation model.

METHODS: Animals were randomly divided into three groups, and intragastrically administered 0-4 °C saline (ice-cold group) or 15-20 °C saline (saline control group) daily for 14 d, or were left untreated (blank control group). Stools were collected 3-24 h after treatment to record the wet and dry weights and the stool form. Intestinal propulsion experiments were carried out and defecation time was measured for six days continuously after suspending treatments. The expressions of PGP9.5 were detected by immunohistochemistry.

RESULTS: Based on the percentage of stool weight changes compared with baseline (before irritation) in 9-14 d, stool weight changes were classified into three levels. Each level shows a different body state, which is state I (no change: plus or minus 5%), state II (slightly decreased: 5%-15%) and state III (decreased: 15%-25%). In state III, between day 9-14, the stool weights decreased by 15%-25% compared with the baseline, and changed at a rate > 10% compared with blank control values, and the stools became small and dry. Additionally, intestinal functions degenerated in these animals, and PGP9.5-positive expression markedly decreased in jejunum, ileum and proximal colon myenteric plexus.

CONCLUSION: Irritation with ice-cold saline is a stable, repeatable method in building constipation model in mice for exploring the pathogenesis and treatment options of constipation, and the change of stool weight and size may serve as a useful tool to judge a constipation model success or not.

Keywords: Cold water, Mouse model, Constipation, ENS

Core tip: Establishing stable animal models is very important for studying disease pathogenesis to develop strategies for prevention and treatment. Evidence from previous researches has shown recurrent and chronic cold water irritation to stomach can inhibit gastrointestinal motility. In this study, we concluded that irritation with ice-cold saline to mice is a stable, repeatable method in building mice constipation model.