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New Model of Acute Pancreatitis

Acute pancreatitis is characterized by intrapancreatic activation of acinar cell-derived digestive enzyme zymogens, acinar cell injury/necrosis, intrapancreatic inflammation, and, in severe cases, acute lung injury. The mechanisms responsible for these changes and the factors regulating their severity are poorly understood but their elucidation could lead to the development of therapeutic strategies designed to alter the morbidity and mortality of pancreatitis.

The researchers in the Boston Pancreas Group and many others have explored these issues using the rodent, secretagogue (i.e. caerulein)-induced model of experimental pancreatitis which is characterized by:

  1. acinar cell vacuolization and injury/necrosis
  2. intra-acinar cell activation of digestive enzyme zymogens such as trypsinogen
  3. intrapancreatic neutrophil sequestration
  4. activation of acinar cell pro-inflammatory transcription factors including NF-kB,
  5. generation of proinflammatory factors including TNF-a.

Caerulein-induced pancreatitis is also associated with an acute lung injury that is characterized by:

  1. intrapulmonary neutrophil sequestration
  2. increased alveolar-capillary membrane permeability
  3. type 2 pneumocyte injury.

Other pancreatitis models include the choline-deficient ethionine containing diet on mice and the arginine administration diet on rat. On rats the intrapancreatic duct infusion of Na-taurocholate has been used successfully as a model of acute pancreatitis. We have adapted this model to mice to take advantage of the various genetically modified mice. Under anesthesia the bilio-pancreatic duct of the mice is exposed and under steady flow Na-Taurocholate is infused into the pancreas by means of a transduodenal injection. The mice are then returned to their cage and allowed to recover. This is a highly reproducible model characterized by intrapancreatic trypsin activation, inflammation and pancreatic necrosis.