Proteases and protease inhibitors in taurocholate-induced acute pancreatitis in rats.

Abstract

Conclusion: Taurocholate-induced acute pancreatitis (AP) in the rat mimics early necrotizing human pancreatitis. Protease activation and protease inhibitor consumption occur consistent with a two-stage development, and contact-phase activation is a possible primary event in this model.

Background: Proteases and protease inhibitors have been indicated to play an important role in both human and experimental acute pancreatitis, although little is known about them in rats.

Methods: Three percent sodium taurocholate was infused into the bilio-pancreatic duct to induce AP, and over 0-72 h we measured lipase, amylase, albumin, prekallikrein, factor X, alpha-1-macroglobulin, alpha-2-antiplasmin, antithrombin III, alpha-1-protease inhibitor, and C1-esterase inhibitor (all in plasma) and histologic and macroscopic findings.

Results: A severe necrotizing, nonlethal, AP was induced with an early increase in plasma lipase and alpha-amylase activity levels and peritoneal exudate followed by a return to near control levels after 72 h. Histologic score and pancreatic wet weight ratio increased initially and remained high during the observation period. The protease inhibitors C1-esterase inhibitor, alpha-2-antiplasmin, and antithrombin III decreased early, within 0-6 h, whereafter levels normalized. The protease inhibitors alpha-1-macroglobulin and alpha-1-protease inhibitor later gradually decreased over the 72 h.