Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2016; 22(10): 2960-2970
Published online Mar 14, 2016. doi: 10.3748/wjg.v22.i10.2960
Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice
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
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
Bin Liu, Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
Author contributions: Zhang H and Liu B contributed equally to design research and write the paper; Xu XF, Jiang TT, Shi YL, Chen Y, Liu F and Zhu LJ performed experiment; Zhang XQ, Gu J and Wu N analyzed data.
Supported by Funds of the National Natural Science Foundation of China, No. 80112725; and Administration of Traditional Chinese Medicine of Shaanxi Province of China, No. jc10.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Shaanxi University of Chinese Medicine.
Conflict-of-interest statement: All authors of this paper declare that there is no any conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhang1227@163.com. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong Zhang, Professor, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Shiji Avenue, Xianyang 712046, Shaanxi Province, China. zhangh1227@163.com
Telephone: +86-29-38183453 Fax: +86-29-38185453
Received: March 25, 2015
Peer-review started: March 27, 2015
First decision: May 18, 2015
Revised: August 12, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: March 14, 2016
Abstract

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 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.

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.

Keywords: Chronic pancreatitis, Fibrosis, Dibutyhin dichloride, Ethanol models, Animal, Pathophysiology

Core tip: It was assured that the model with chronic fibrotic lesions in pancreas was induced by single intravenous injection of dibutyltin dichloride (DBTC) and additional daily ethanol ingestion. But until now, all experiments about the animal model induced by DBTC just have been performed in rat. However, there are some differences in the structure of bile ducts between rat and mouse. As we known, rat has no gall bladder, but mouse’s gall bladder structure is similar to humans’. So we adopted DBTC injection joint long-term consumption of ethanol to observe whether chronic pancreatitis could be induced in mice and the related pathophysiology.