Ligation of the common bile-pancreatic duct induces
hyperamylasemia and
acute pancreatitis in rats. Pancreatic morphologic changes include
edema, acinar cell damage, and mild
inflammation. The pathogenesis of
acute pancreatitis in this model is not understood, but may involve altered secretion and intrapancreatic activation of acinar
proteases. We hypothesized that
trypsinogen activation, measured by the production of 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 dissected but not ligated (
sham). Rats were killed after 6, 24, and 48 hr. Serum
amylase was measured and histologic sections were analyzed for morphologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal. anti-TAP antibody in an
enzyme-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreatic duct
ligation,
hyperamylasemia and acute morphologic changes of
acute 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
ligation compared to those of
sham. We conclude that increased intrapancreatic
trypsinogen activation occurs early in this form of experimental
acute pancreatitis and that it occurs prior to evidence of acinar cell destruction. These data and observations support the possibility that intrapancreatic
protease activation contributes to the pathogenesis of
ligation-induced
acute pancreatitis.