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

Int J Pancreatol. 1999 Apr;25(2):113-21. doi: 10.1385/IJGC:25:2:113.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithrombin III / metabolism
  • Complement C1 Inactivator Proteins / metabolism
  • Disease Models, Animal
  • Endopeptidases / metabolism*
  • Humans
  • Lipase / blood
  • Male
  • Pancreatitis, Acute Necrotizing / chemically induced
  • Pancreatitis, Acute Necrotizing / enzymology
  • Pancreatitis, Acute Necrotizing / metabolism*
  • Protease Inhibitors / metabolism*
  • Rats
  • Rats, Wistar
  • Taurocholic Acid / toxicity
  • Time Factors
  • alpha 1-Antitrypsin / metabolism
  • alpha-2-Antiplasmin / metabolism
  • alpha-Amylases / blood
  • alpha-Macroglobulins / metabolism

Substances

  • Complement C1 Inactivator Proteins
  • Protease Inhibitors
  • alpha 1-Antitrypsin
  • alpha-2-Antiplasmin
  • alpha-Macroglobulins
  • Taurocholic Acid
  • Antithrombin III
  • Lipase
  • alpha-Amylases
  • Endopeptidases