Therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis

Objective: To assess the therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis (SAP). Methods: Forty-two 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 in 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, which was 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. Survied 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 (215.50±58.52)U/L, (372.17±38.05)U/L, (276.77±44.92)pg/ml at 6 h, (396.67±70.29)U/L, (548.50±75.29)U/L, (308.99±34.95)pg/ml at 12 h, (425.17±86.33)U/L, (665.83±84.05)U/L, (311.60±46.51)pg/ml, respectively, which were increased significantly (P0.01, vs HC). In SAP-ICE-I group, their levels were decreased significantly (P0.01, 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 (P0.01, vs HC). The expressions of IL-1β and IL-18 mRNA were decreased significantly in SAP-ICE-I group (P0.01, vs SAP-S), whereas Caspase-1 mRNA expressions had no significant differences (P0.05). Caspase-1 inhibition had no effect on the severity of liver tissue damage. Conclusion: Caspase-1 activate cytokines, IL-1β and IL-18, play a pivotal role in the course of liver injury in SAP. Caspase-1 inhibitor can improve liver functions effectively.