Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition

BACKGROUND:Emodin,a traditional Chinese medicine,has a therapeutic effect on severe acute pancreatitis(SAP),whereas the underlying mechanism is still unclear.Studies showed that the intestinal mucosa impairment,and subsequent release of endotoxin and proinflammatory cytokines such as IL-1β,which further leads to the dysfunction of multiple organs,is the potentially lethal mechanism of SAP.Caspase-1,an IL-1β-converting enzyme,plays an important role in this cytokine cascade process.Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP.METHODS:Eighty Sprague-Dawley rats were randomly divided into four groups(n=20 each group):SAP,sham-operated(SO),emodin-treated(EM) and caspase-1 inhibitor-treated(ICE-I) groups.SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct.Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction.Serum levels of IL-1β,IL-18 and endotoxin,histopathological alteration of pancreas tissues,intestinal mucosa,and the intestinal caspase-1 m RNA and protein expressions were assessed 24 hours after SAP induction.RESULTS:Rats in the SAP group had higher serum levels of IL-1β and IL-18(P<0.05),pancreatic and gut pathological scores(P<0.05),and caspase-1 m RNA and protein expressions(P<0.05) compared with the SO group.Compared with the SAP group,rats in the EM and ICE-I groups had lower IL-1β and IL-18 levels(P<0.05),lower pancreatic and gut pathological scores(P<0.05),and decreased expression of intestine caspase-1 m RNA(P<0.05).Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions,more disappeared intercellular joints,and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups.CONCLUSIONS:Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP.Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines,including IL-1β and IL-18.Our animal data may be applicable in clinical practice.