A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

Abstract

Background: Suitable experimental models of gallstone pancreatitis with systemic inflammation and mortality are limited. We developed a novel murine model of duct-ligation-induced acute pancreatitis associated with multiorgan dysfunction and severe mortality. Methods: Laparotomy was done on C57/BL6 mice followed by pancreatic duct (PD) ligation, bile duct (BD) ligation without PD ligation, or sham operation. Results: Only mice with PD ligation developed acute pancreatitis and had 100% mortality. Pulmonary compliance was significantly reduced after PD ligation but not BD ligation. Bronchoalveolar lavage fluid neutrophil count and interleukin-1 β concentration, and the plasma creatinine level, were significantly elevated with PD ligation but not BD ligation. Pancreatic nuclearfactor kB (p65) and activator protein 1 (c-Jun) were activated within 1 h of PD ligation. Conclusion: PD-ligation-induced acute pancreatitis in mice is associated with systemic inflammation, acute lung injury, multiorgan dysfunction and death. The development of this novel model is an exciting and notable advance in the field.