Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis.METHODS: The mice were randomly divided into 2 groups(n = 50), control group and model group. The mice in model group were given ethanol(10%) in drin...

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Published in:World journal of gastroenterology : WJG 2016-03, Vol.22 (10), p.2960-2970
Main Authors: Zhang, Hong, Liu, Bin, Xu, Xiao-Fan, Jiang, Ting-Ting, Zhang, Xiao-Qin, Shi, Ying-Li, Chen, Yu, Liu, Fang, Gu, Jie, Zhu, Lin-Jia, Wu, Nan
Format: Article
Language:English
Subjects:
Animals
Basic Study
Biomarkers - blood
Chronic
dichloride
Ethanol
Disease Models, Animal
Ethanol
Fibrosis
Gene Expression Regulation
Matrix Metalloproteinase 13 - genetics
Matrix Metalloproteinase 13 - metabolism
Mice
models
Animal
Pathophysiology
Organotin Compounds
Pancreas - metabolism
Pancreas - pathology
Pancreas - physiopathology
Pancreatitis, Chronic - blood
Pancreatitis, Chronic - chemically induced
Pancreatitis, Chronic - pathology
Pancreatitis, Chronic - physiopathology
pancreatitis
Fibrosis
Dibutyhin
Time Factors
Tissue Inhibitor of Metalloproteinase-1 - metabolism
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Summary:AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis.METHODS: The mice were randomly divided into 2 groups(n = 50), control group and model group. The mice in model group were given ethanol(10%) in drinking water after injection of dibutyltin dichloride(DBTC)(8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein( 60 % ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin(FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen typeⅠ(COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinases-1(TIMP-1) m RNA in the pancreas was assessed by real time PCR.RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group(P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 m RNA in pancreas decreased, but TIMP-1 m RNA increased at model group.CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v22.i10.2960