Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2019; 11(12): 1115-1125
Published online Dec 15, 2019. doi: 10.4251/wjgo.v11.i12.1115
Improved method for inducing chronic atrophic gastritis in mice
Xian Wei, Xue-Ping Feng, Lu-Yao Wang, Yan-Qiang Huang, Ling-Ling Liang, Xiao-Qiang Mo, Hong-Yu Wei
Xian Wei, Xue-Ping Feng, Lu-Yao Wang, Yan-Qiang Huang, Ling-Ling Liang, Xiao-Qiang Mo, Hong-Yu Wei, Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China.
Author contributions: Wei X and Feng XP performed the research and contributed equally to this work; Wang LY, Liang LL, Mo XQ, and Wei HY analyzed the data; Huang YQ designed the research and analyzed the data; all authors drafted the article, made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by National Natural Science Foundation of China, No. 31460023; Science Research and Technology Development Project of Guangxi, No. 1598025-33.
Institutional review board statement: All specimens from the patients were obtained after informed consent and ethical permission were obtained for participation in the study.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yan-Qiang Huang, MD, PhD, Professor, Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, No. 98, Countryside Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. hyq77615@163.com
Telephone: +86-776-2849490 Fax: +86-776-2853272
Received: May 16, 2019
Peer-review started: May 21, 2019
First decision: July 31, 2019
Revised: August 5, 2019
Accepted: October 1, 2019
Article in press: October 1, 2019
Published online: December 15, 2019
Processing time: 208 Days and 17.2 Hours
Abstract
BACKGROUND

Chronic atrophic gastritis (CAG) is a common disease of the digestive system with pathological characteristics of a decreasing number, or disappearance, of inherent glands of the gastric mucosa. CAG has been defined as a precancerous condition of gastric cancer. Intestinal metaplasia or intraepithelial neoplasia accompanying atrophied glands of the stomach is regarded as one of the most important precancerous lesions of gastric cancer. As a common malignant tumour, gastric cancer remains without a satisfactory therapy and its pathogenesis remains unclear, seriously threatening human life. Therefore, some scholars have proposed to prevent the incidence of gastric cancer by avoiding precancerous lesions. If CAG can be reversed, the incidence of gastric cancer can be substantially reduced. To reverse and prevent CAG and study its pathogenesis and therapy, it is necessary to develop an ideal, safe, stable, animal model.

AIM

To study a rapid, stable, and safe method of establishing a mouse model of human CAG.

METHODS

Six-week-old Kunming mice were divided into a phosphate buffered solution control group, a Helicobacter pylori (H. pylori) group, an N-methyl-N'-nitroguanidine (MNNG) group, an ammonia water group, and a group combining H. pylori, MNNG, and ammonia water (hereinafter referred to as the combined group). The mice were administrated with drinking water containing ammonia or infected with H. pylori through gavage. At the 30th, 60th, 90th, and 120th day after the last H. pylori infection, mice were selected randomly to collect their gastric mucosa for hematoxylin eosin staining, terminal nick-end labelling staining detection, and immunohistochemical staining for Bax and Bcl-2. In addition, H. pylori was isolated, cultured, and identified, and its extent of colonisation calculated. Blood was collected to detect inflammatory factors interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α and immune function markers CD4 and CD8 to confirm successful establishment of the CAG model.

RESULTS

The combined group showed slight CAG at the 90th day and moderate CAG at the 120th day, while other groups did not show CAG at that time.

CONCLUSION

The combination of H. pylori, MNNG, and ammonia is an effective method of developing a mouse model of human CAG.

Keywords: Method; Chronic atrophic gastritis; Mice; Helicobacter pylori; N-methyl-N'-nitroguanidine; Ammonia water

Core tip: A chronic atrophic gastritis (CAG) model was successfully established at the 90th day after the last Helicobacter pylori (H. pylori) infection of six-week-old mice, with a success rate reaching 90%. The method overcomes the difficulty in colonising H. pylori in mice and the fact that the colonisation time is short. In addition, rats are replaced with mice, and the method is thus simpler and also cheaper. The established models are stable and safe, therefore, the method is a relatively ideal method for establishing a mouse model of CAG. It provides a significant help when exploring the mechanisms of occurrence and prevention CAG.