The Relationship Between Caspase-1 / IL-1β Axis And Intestinal Dysfunction In Inflammatory Bowel Disease

Objective: To investigate the relationship between Caspase-1/ IL-1β axis and intestinal dysfunction in inflammatory bowel disease(IBD).Methods: The isolated intestine of mice with normal,acute enteritis,chronic enteritis and chronic colitis-associated cancer(CAC)was used as the research object.Acetylcholine(Ach)was acted as stimulation,and biological signal acquisition and processing system was applied to study the changes of isolated intestinal contractility under different physiological and pathological conditions.The expression of Caspase-1 and IL-1β in intestine and plasma of normal,acute enteritis,chronic enteritis and CAC was detected by immunohistochemical method,ELISA and Western blot.Results:1.General condition of normal,acute enteritis,chronic enteritis and CAC mice.Normal mice had active mind,smooth hair,normal diet,continuous weight gain and normal stool.Acute enteritis,chronic enteritis and CAC mice were poorer in mental state,hair color and diet than normal mice,and their weight was also lower,and stool traits were changed,the fecal occult blood test(OBT)was positive.Typical histological features of the intestine in different pathological states can be observed by HE staining.2.The expression of IL-1β in plasma of mice.ELISA showed that the plasma IL-1β levels of acute enteritis,chronic enteritis and CAC was higher than that of normal mice.IL-1β in plasma of normal,acute enteritis,chronic enteritis and CAC mice were 32.631±12.564 pg/ml,103.609±7.639 pg/ml,89.762±7.542 pg/ml,60.859±8.005 pg/ml,and the difference was statistically significant(P<0.05).3.Contractility of the isolated intestine of mice.Without stimulation,the contractile amplitude of isolated intestine with acute enteritis,chronic enteritis and pericarcinomatous was lower than that with normal mice,however,which with CAC was higher(P<0.05).The contractile amplitude of intestine with normal,acute enteritis,chronic enteritis,CAC and pericarcinomatous were 0.181±0.012 g,0.161±0.007 g,0.161±0.008 g,0.219±0.033 g,0.149±0.006 g.With 1μM of acetylcholine,the contractile amplitude of isolated intestine with acute enteritis,chronic enteritis,CAC and pericarcinomatous was higher than that with normal mice(P<0.05).The contractile amplitude of intestine with normal,acute enteritis,chronic enteritis,CAC and pericarcinomatous were 0.196±0.057 g,0.369±0.037 g,0.391±0.091 g,0.431±0.052 g,0.348±0.046 g.4.The expression of Caspase-1 in intestinal tissues of mice.Immunohistochemical staining showed that the expression of Caspase-1 in the mucosa and muscle of acute enteritis and chronic enteritis was higher than that of normal mice.In the mucosa of CAC,the expression of Caspase-1 was lower than normal mice,but which in the muscle of CAC was higher(P<0.05).The expression of Caspase-1 in the mucosa of normal,acute enteritis,chronic enteritis and CAC were 0.195±0.01,0.287±0.01,0.221±0.01,0.178±0.01.The results of Western blot showed that the expression of Caspase-1 in the mucosa of acute enteritis and chronic enteritis was higher than that of normal mice,but which of CAC was lower(P<0.05).The expression of Caspase-1 in mucosa of normal,acute enteritis,chronic enteritis and CAC were 0.942±0.199,1.831±0.641,2.077±0.817,0.665±0.155.The expression of Caspase-1 in the muscle of acute enteritis,chronic enteritis and CAC was higher than that of normal mice(P<0.05).The expression of Caspase-1 in muscle of normal,acute enteritis,chronic enteritis,CAC and pericarcinomatous were 0.806±0.061,1.209±0.056,1.082±0.048,0.962±0.093,0.908±0.073.Conclusion:1.Intestinal inflammation leads to bowel motility dysfunction through the Caspase-1 / IL-1β axis,increasing sensitivity to stimulation.2.Caspase-1 and IL-1β levels may be a valuable biomarker for assessment of inflammatory bowel disease.