A novel animal model of severe pancreatitis in mice and its differences to the rat

作者：Hartwig Werner^*; Schimmel Eik; Hackert Thilo; Fortunato Franco; Bergmann Frank; Baczako Andrea; Strobel Oliver; Buechler Markus W; Werner Jens

来源：Surgery, 2008, 144(3): 394-403.

DOI：10.1016/j.surg.2008.04.006

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) ware 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)-1 alpha, and IL-1 beta 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 studies in transgenic mice.

• 出版日期2008-9