Proteases and Protease Inhibitors in Cerulein-Induced Acute Pancreatitis in Rats

Abstract

Background. Proteases and protease inhibitors are important in acute pancreatitis (AP), although little is known about the time course in cerulein-induced AP in the rat.Materials and methods. AP was induced by supramaximal stimulation of cerulein, 10 μg/kg/h, and during 72 h we measured lipase, amylase, albumin, prekallikrein, factor X, α1-protease inhibitor, α1-macroglobulin, α2-antiplasmin, antithrombin III (all in plasma) and macroscopic and histologic variables.Results. Within 12 h an edematous pancreatitis was evident with peak values of peritoneal exudate, pancreatic wet weight ratio, and plasma amylase and lipase activities. Histologically, edema and vacuolization were prominent already after 3 and 6 h, respectively, while inflammation, necrosis, and total histological score gradually increase to reach peak levels at 48 h. Proenzymes and most plasma protease inhibitors decreased to low levels after 6–12 h followed by a gradual increase. The sequential changes over time indicate that kallikrein - kinin activation, and plasminogen activation are probably early events in cerulein-induced AP in rats. α1-Macroglobulin and α1-protease inhibitor gradually decreased during the whole study period, probably being “second line” defense inhibitors. Levels above normal were seen for α2-antiplasmin and factor X at 48 h, normalizing at 72 h.Conclusions. These results suggest that protease activation and protease inhibitor consumption occur in cerulein-induced AP in the rat.