Dynamic Changes Of IL-17, Occludin And ZO1 In Mice With Post-infectious Irritable Bowel Syndrome

BackgroundIrritable bowel syndrome(IBS)is a common functional gastrointestinal disorder characterized by chronic abdominal symptoms,about 10% of which after recovery from acute infection is now defined as one subgroup of postinfectiously IBS(PI-IBS).The aetiology of PI-IBS remains unknown,but now it may be related to microbial dysbiosis,low-grade inflammation in intestinal mucosa,mucosal immune activation and increased mucosal permeability.IL-17,as a kind of important cytokines,has a dual role of proinflammatory and anti-inflammatory,the dynamic change of which have played an important role in a variety of autoimmune diseases and infectious diseases.In our previous study found that IL-17 increased in peripheral blood and intestinal mucosa tissue of PI-IBS.But until now,there are no related literatures report whether does IL-17 have a dynamic change from the original intestinal infection to the development of PI-IBS.And there is rare literature reports whether there is damage to intestinal mucosal barrier of PI-IBS.ObjectiveThe purpose of this study was to establish PI-IBS animal model usingC57BL/6 mice infected by Trichinella Spiralis,further to observe the changes of visceral hypersensitivity and mucosal permeability by the abdominal withdrawal reflex(AWR)and the percentage of fecal water content at week 2,4,6 and 8 after infection,and to observe the dynamic changes of intestinal IL-17,occludin and ZO-1 in mice with post-infectious irritable bowel syndrome(PI-IBS).MethodsForty C57BL/6 mice were randomly divided into 5 groups:control group and infection groups(2 weeks,4 weeks,6 weeks and 8 weeks after trichinella infection).Infection groups were given by gavaging of 400~500Trichinella spiralis in 0.2 mL of normal saline.The body weight of mice were recorded at week 2,4,6 and 8 after infection.The visceral sensitivity of mice was measured by the abdominal withdrawal reflex(AWR).The stool was collected continuously for 8 hours to calculate the percentage of fecal water content.Pathological changes of gut were observed by HE staining.The expressions of IL-17,occludin and ZO-1 in ileocecus and colon were detected by immunohistochemistry and Western blotting.Results(1)At week 2 after infection,the acute inflammation of the intestinal tract was observed and the body weight of mice were significantly decreased(P=0.000).Until week 8 after infection,the intestinal inflammation and body weight of mice recovered to normal.(2)When the colorectal dilatation capacity was 0.35 and 0.5 mL,the AWR scores in the infection groups were significantly higher than those in the control group(P<0.01).The percentages of fecal water content in the infection groups were significantly higher than those in the control group(P<0.05).(3)Compared with the control group,the expressions of IL-17 were significantly decreased in week 2 group(P<0.05)and increased in week 8group(P<0.05).The expressions of occludin and ZO-1 in the infection groups were significantly lower than those in the control group(P<0.05).Conclusion(1)C57BL/6 mice infected by Trichinella Spiralis,the visceral sensitivity and intestinal mucosal permeability increased,which could well simulate the symptoms of PI-IBS,indicating that the model was suitable for the animal model of PI-IBS.(2)After Trichinella infection in C57BL/6 mice,the dynamic changes of IL-17 in ileocecal and colon decreased first and then increased.(3)After Trichinella spiralis infected C57BL/6 mice,the tight junction proteins occludin and ZO-1 in ileocecal and colon decreased.(4)The dynamic changes of IL-17 and the decrease of Tight junction proteins may be one of the mechanisms of visceral hypersensitivity and increased percentages of fecal water content.They may be involved in the development of PI-IBS.