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An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein.

Ahmadi A, Nikkhoo B, Mokarizadeh A, Rahmani MR, Fakhari S, Mohammadi M, Jalili A - Cent Eur J Immunol (2016)

Bottom Line: 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).IP injections of ethanol provide higher reproducibility compared to ethanol feeding.Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing new therapies.

View Article: PubMed Central - PubMed

Affiliation: Student Research Committee, Kurdistan Cellular and Molecular Research Centre, Kurdistan University of Medical Sciences, Sanandaj, Iran.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus

Expression of inflammatory (IL-1 and TNF-a), fibrogenic cytokines (TGF-), and the marker of activated pancreatic stellate cells (a-SMA) in the pancreata of studied groups by real-time RT-PCR analysis. Presented boxes and bars indicate mean ± SEM (n = 8)
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Figure 0007: Expression of inflammatory (IL-1 and TNF-a), fibrogenic cytokines (TGF-), and the marker of activated pancreatic stellate cells (a-SMA) in the pancreata of studied groups by real-time RT-PCR analysis. Presented boxes and bars indicate mean ± SEM (n = 8)

Mentions: Quantitative real-time RT-PCR analyses (Fig. 7) showed that the expression of mRNA of inflammatory cytokines (IL-1β and TNF-α) were significantly increased in the pancreas tissue of Cer and Et-Cer mice compared to Ctrl (p < 0.05). As depicted in Fig. 7, these increases were higher in Et-Cer mice than in the Cer group, but they were not statistically significant (p = 0.80 and p = 97, respectively).


An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein.

Ahmadi A, Nikkhoo B, Mokarizadeh A, Rahmani MR, Fakhari S, Mohammadi M, Jalili A - Cent Eur J Immunol (2016)

Expression of inflammatory (IL-1 and TNF-a), fibrogenic cytokines (TGF-), and the marker of activated pancreatic stellate cells (a-SMA) in the pancreata of studied groups by real-time RT-PCR analysis. Presented boxes and bars indicate mean ± SEM (n = 8)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829821&req=5

Figure 0007: Expression of inflammatory (IL-1 and TNF-a), fibrogenic cytokines (TGF-), and the marker of activated pancreatic stellate cells (a-SMA) in the pancreata of studied groups by real-time RT-PCR analysis. Presented boxes and bars indicate mean ± SEM (n = 8)
Mentions: Quantitative real-time RT-PCR analyses (Fig. 7) showed that the expression of mRNA of inflammatory cytokines (IL-1β and TNF-α) were significantly increased in the pancreas tissue of Cer and Et-Cer mice compared to Ctrl (p < 0.05). As depicted in Fig. 7, these increases were higher in Et-Cer mice than in the Cer group, but they were not statistically significant (p = 0.80 and p = 97, respectively).

Bottom Line: 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).IP injections of ethanol provide higher reproducibility compared to ethanol feeding.Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing new therapies.

View Article: PubMed Central - PubMed

Affiliation: Student Research Committee, Kurdistan Cellular and Molecular Research Centre, Kurdistan University of Medical Sciences, Sanandaj, Iran.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus