Abstract: AIM: To assess the protective effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis (SAP).METHODS: Fortytwo SD rats were randomly divided into 3 groups: healthy controls (HC, n=6);SAP-S group (n=18);SAP-ICE-I group (n=18).SAP was induced by retrograde infusion of 5% sodium taurocholate into the bili-pancreatic duct of SD rats.HC rats underwent same surgical procedures and duct cannulation without sodium taurocholate.In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and repeated after 12 h. In SAP-ICE-I group, rats were firstly given ICE inhibitor intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, this was repeated at 12 h.Surviving rats were killed at certain time points, and all samples were obtained for subsequent analysis.RESULTS: The serum levels of ALT, AST and IL-1β in SAP-S group were (215±58), (372±38) U/L, (277±45) pg/mL at 6 h, (397±70), (548±75) U/L, (309±35) pg/mL at 12 h, (425±86), (666±84) U/L, (312±46) pg/mL at 18 h, respectively, which were increased significantly (P<0.01 vs HC).In SAP-ICE-I group, their levels were decreased significantly (P<0.01 vs SAP-S).Intrahepatic expressions of Caspase-1, IL-1β and IL-18 mRNA could be observed in HC, which were increased significantly in SAP-S group (P<0.01 vs HC).The expressions of IL-1β and IL-18 mRNA were decreased significantly in SAP-ICE-I group (P<0.01 vs SAP-S), whereas Caspase-1 mRNA expression had no significant differences (P>0.05).CONCLUSION: Caspase-1 activation, and the over production of IL-1β and IL-18may play pivotal roles in the pathogenesis of liver injury and Caspase-1 inhibitor improves liver functions effectively in experimental SAP.

Key words: severe acute pancreatitis, liver injury, Caspase-1, Interleukin-1β, Interleukin-18