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

Summary 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, α-1-macroglobulin, α-2-antiplasmin, antithrombin III, α-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 α-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, α-2-antiplasmin, and antithrombin III decreased early, within 0–6 h, whereafter levels normalized. The protease inhibitors α-1-macroglobulin and α-1-protease inhibitor later gradually decreased over the 72 h. 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.