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 SAPS 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 ( 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-18mRNA were decreased significantly in SAP-ICE-I group ( P ＜ 0.01, vs SAP-S), whereas Caspase-1 mRNA expressions had no significant differences ( P ＞ 0.05). 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.