An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein.
BACKGROUND
Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treated with cerulein or ethanol alone.


METHODS
Thirty-two male C57BL/6 mice were randomly selected, divided into four groups, and treated intraperitoneally with saline (10 ml/kg, control group), ethanol (3 g/kg; 30% v/v), cerulein (50 µg/kg), or ethanol + cerulein, for six weeks. Histopathological and immunohistochemical assays for chronic pancreatitis index along with real-time PCR assessments for mRNA levels of inflammatory cytokines and fibrogenic markers were conducted to verify the CP induction.


RESULTS
The results indicated that CP index (CPI) was significantly increased in ethanol-cerulein mice compared to the saline, ethanol, and cerulein groups (p < 0.001). Interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), α-smooth muscle actin (α-SMA), and myeloperoxidase activity were also significantly greater in both cerulein and ethanol-cerulein groups than in the saline treated animals (p < 0.001). Immunohistochemical analysis revealed enhanced expression of TGF-β and α-SMA in ethanol-cerulein mice compared to the saline group.


CONCLUSIONS
Intraperitoneal (IP) injections of ethanol and cerulein could successfully induce CP in mice. IP injections of ethanol provide higher reproducibility compared to ethanol feeding. The model is simple, non-invasive, reproducible, and time-saving. Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing new therapies.
Student Research Committee, Kurdistan Cellular and Molecular Research Centre, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Abbas
A
Ahmadi
Department of Pathology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Bahram
B
Nikkhoo
Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Aram
A
Mokarizadeh
Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Mohammad-Reza
MR
Rahmani
Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Shohreh
S
Fakhari
Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Mehdi
M
Mohammadi
Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Ali
A
Jalili
cerulein; chronic pancreatitis; ethanol; fibrosis; mouse model