title: Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.
abstract: OBJECTIVE
  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 type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA 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 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Shi
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Lin-Jia
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Hong Zhang, Bin Liu, Xiao-Fan Xu, Ting-Ting Jiang, Xiao-Qin Zhang, Ying-Li Shi, Yu Chen, Fang Liu, Jie Gu, Lin-Jia Zhu, Nan Wu, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D000431:Ethanol; D005355:Fibrosis; D005786:Gene Expression Regulation; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009947:Organotin Compounds; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009947:Organotin Compounds; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D000431:Ethanol; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C020735:dibutyldichlorotin
keywords: Animal; Chronic pancreatitis; Dibutyhin dichloride; Ethanol models; Fibrosis; Pathophysiology