【Animal Modeling】-Preparation of a mouse model of diarrhea-type irritable bowel syndrome induced by acetic acid combined with restraint stress

  Objective To establish a mouse model of diarrhea-predominant irritable bowel syndrome by rectal infusion of 3% acetic acid (AA) combined with restraint stress, and to evaluate the feasibility of the model.

  Methods Forty-five male C57BL/6J mice were divided into healthy control group (group C), 3% acetic acid group (group A), and 3% acetic acid + restraint group (group A+R). The weight changes and survival of the mice in each group before and after the intervention were compared, as well as the fecal water content, the transit time of the whole intestine, and the visceral pain threshold after the intervention, and the advantages and disadvantages of the two modeling methods were compared. The pathological changes of colon in groups C and A+R were observed, FD4 penetration test was used to evaluate the integrity of the intestinal mucosa of mice, ELISA was used to detect the content of serum 5-HT and TNF-α, and immunohistochemistry was used to detect the colon tissue. The expression of 5-HTR3A can clarify the pathological characteristics of this modeling method.

  Results Compared with group C, the visceral pain threshold and fecal water content in group A+R were significantly increased (P<0.001); the transit time of the whole intestinal tract was significantly shortened (P<0.05), while the visceral pain threshold and fecal content in group A were significantly increased (P<0.001). Although the amount of water was also significantly decreased (P < 0.05), the transit time of the whole intestine only had a trend of change, and there was no significant difference (P>0.05). In A+R group, the content of FD4 in plasma was significantly increased (P<0.001), the content of 5-HT and TNF-α in serum was significantly increased (P<0.05), and the expression of 5-HTR3A in colon tissue was also significantly increased (P<0.001) .

  Conclusion Compared with 3% acetic acid enema, 3% acetic acid enema combined with restraint stress can better simulate the local symptoms of IBS-D patients, and can simulate related pathological changes.