Background
Unlike edematous pancreatitis, induction of severe necrotizing pancreatitis in rats
generally requires an invasive laparotomy with infusion and/or ligation of the pancreatic
duct or duodenal or arterial occlusion. The aim of this study was to establish and
characterize a noninvasive model of severe acute pancreatitis in rats.
Methods
Wistar rats were infused intravenously with cerulein or a combination of cerulein
and enterokinase. Saline (154-mmol/L NaCl) or enterokinase only was infused in controls.
In a first set of experiments, intrapancreatic protease activation and the release
of cytokines were correlated with the severity of organ injury. Pancreatic and pulmonary
injuries were determined at 6 h. In a second set of experiments, we assessed 24-h
survival, serum parameters possibly reflecting the course of the disease, and morphologic
changes later in the course of the disease.
Results
The severity of pancreatic injury and survival were correlated strongly with the amount
of enterokinase infused simultaneously with cerulein. Trypsin as well as elastase
and cathepsin B activity in pancreatic tissue samples were increased markedly in these
animals. Marked pancreatic hemorrhage, necrosis, and leukocyte infiltration were present
in animals with the greatest amounts of enterokinase infused. IL-6 and LDH, but not
IL-1β, CRP, and amylase, in serum correlated with the severity of pancreatitis.
Conclusions
This noninvasive rat model of acute pancreatitis is characterized by major pancreatic
necrosis, hemorrhage, and fatality. The simple and noninvasive induction technique
may have advantages for future studies on inflammatory changes and sepsis in necrotizing
pancreatitis compared with other currently available invasive models.
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Article info
Publication history
Accepted:
April 15,
2007
Identification
Copyright
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
