LIGATION-INDUCED ACUTE-PANCREATITIS INCREASES PANCREATIC AND CIRCULATING TRYPSINOGEN ACTIVATION PEPTIDES

Ligation of the common bile-pancreatic duct induces hyperamylasemia an d acute pancreatitis in rats. Pancreatic morphologic changes include e dema, acinar cell damage, and mild inflammation. The pathogenesis of a cute pancreatitis in this model is not understood, but may involve alt ered secretion and intrapancreatic activation of acinar proteases. We hypothesized that trypsinogen activation, measured by the production o f plasma and pancreatic trypsinogen activation peptides (TAP), occurs early in this model. We performed the following experiments: rats were prepared with (1) bile-pancreatic ducts ligated and (2) ducts dissect ed but not ligated (sham). Rats were killed after 6, 24, and 48 hr. Se rum amylase was measured and histologic sections were analyzed for mor phologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal anti-TAP antibody in an enzym e-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreati c duct ligation, hyperamylasemia and acute morphologic changes of acut e pancreatitis were observed. Evidence of acinar cell destruction was not evident until 48 hr after ligation. Levels of serum and pancreatic tissue TAP were significantly elevated at both 24 and 48 hr after lig ation compared to those of sham. We conclude that increased intrapancr eatic trypsinogen activation occurs early in this form of experimental acute pancreatitis and that it occurs prior to evidence of acinar cel l destruction. These data and observations support the possibility tha t intrapancreatic protease activation contributes to the pathogenesis of ligation-induced acute pancreatitis. (C) 1996 Academic Press, Inc.