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

Background. Proteases and protease inhibitors have been indicated to play a n important role in both human and experimental acute pancreatitis, althoug h little is known about them in rats. Methods. Three percent sodium taurocholate was infused into the bilio-pancr eatic duct to induce AP, and over 0-72 h we measured lipase, amylase, album in, prekallikrein, factor X, alpha-1-macroglobulin, alpha-2-antiplasmin, an tithrombin 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 incr ease in plasma lipase and alpha-amylase activity levels and peritoneal exud ate followed by a return to near control levels after 72 h. Histologic scor e and pancreatic wet weight ratio increased initially and remained high dur ing the observation period. The protease inhibitors C1-esterase inhibitor, alpha-2-antiplasmin, and antithrombin III decreased early, within 0-6 h, wh ereafter levels normalized. The protease inhibitors alpha-1-macroglobulin a nd alpha-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 inhi bitor consumption occur consistent with a two-stage development, and contac t-phase activation is a possible primary event in this model.