Background
A noninvasive model of necrohemorrhagic pancreatitis induced by simultaneous intravenous
cerulein/enterokinase (EK) infusion has recently been established in rats. The aim
of the present study was to establish this new model in mice and to compare it with
the rat model.
Methods
Male Balb/C mice (20 to 25 g) were used for the experiments. Pancreatitis was induced
by simultaneous intravenous infusion of cerulein and EK. Controls were infused with
either 0.9% NaCl, cerulein, or EK. Animals were humanely killed 6 hours after start
of infusions. Pancreatic and pulmonary injury was assessed by histology, wet-to-dry
weight ratio, and myeloperoxidase activity. Systemic cytokine, amylase, and lactate
dehydrogenase (LDH) levels in blood were measured to assess pancreatic and systemic
inflammatory response. To evaluate the role of protease activity in this model, trypsin,
cathepsin B, and elastase activity were measured in pancreatic tissue. Survival experiments
were performed to determine survival time and tissue injury in the later course of
the disease.
Results
Mice with simultaneous cerulein/EK infusion developed marked local and systemic organ
injury compared with those animals who received cerulein or EK alone. Pancreatic and
pulmonary injury increased with high concentrations of cerulein/EK infusions. Survival
decreased in these animals. Whereas acinar cell apoptosis was an early finding, pancreatic
necrosis was observed later in the course of the disease. Serum levels of LDH, interleukin
(IL)-1α, and IL-1β reflected cell damage and the systemic inflammatory response. Protease
activity in pancreatic tissue was greatest in animals with simultaneous cerulein/EK
infusion.
Conclusions
Using intravenous cerulein/EK infusions, a model of lethal acute pancreatitis has
been established in mice. Major pancreatic edema, acinar cell apoptosis and necrosis,
and pulmonary leukocyte sequestration are characteristic findings in this model. Although
pancreatic injury was not as strong as in the rat model, this model may prove useful
for future studies in transgenic mice.
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Article info
Publication history
Published online: July 24, 2008
Accepted:
April 8,
2008
Footnotes
Supported by a grant from the Heidelberger Stiftung Chirurgie to W.H.
Identification
Copyright
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
