Histological evaluation and analysis of intestinal flora in a rat model of colitis-cancer transformation induced by azoxymethane/dextran sulfate sodium
10.3969/j.issn.1005-4847.2024.11.001
- VernacularTitle:AOM/DSS诱导建立结肠炎-癌转化大鼠模型的组织学评价及肠道菌群分析
- Author:
Xiunan WEI
1
;
Dajuan SUN
;
Junwei LIANG
;
Jiahui LIU
;
Gongyi LI
;
Lili CHI
Author Information
1. 山东中医药大学第一临床医学院,济南 250014
- Publication Type:Journal Article
- Keywords:
colitis associated colorectal cancer;
colitis-cancer transformation;
histopathology;
16S rRNA sequencing;
intestinal flora
- From:
Acta Laboratorium Animalis Scientia Sinica
2024;32(11):1369-1378
- CountryChina
- Language:Chinese
-
Abstract:
Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.
