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Am J Physiol Gastrointest Liver Physiol. 2018 Mar 1;314(3):G349-G359. doi: 10.1152/ajpgi.00124.2017. Epub 2017 Dec 6.

Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree.

Berntsen NL1,2,3, Fosby B1,4, Valestrand L1,2,3, Tan C1, Reims HM5, Schrumpf E1,2,3, Karlsen TH1,2,3,6,7, Line PD4,7, Melum E1,2,3,6.

Author information

1
Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway.
2
Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway.
3
K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway.
4
Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway.
5
Department of Pathology, Oslo University Hospital Rikshospitalet , Oslo , Norway.
6
Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway.
7
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway.

Abstract

Cholangiopathies are progressive disorders with largely unknown pathoetiology and limited treatment options. We aimed to develop a novel surgical technique with direct access to the bile ducts that would complement existing mouse models of cholestasis, biliary inflammation, and fibrosis and present a new route of administration for testing of potential treatment strategies. We developed a surgical technique to access the murine biliary tree by injection of different solvents through catheterization of the gall bladder with simultaneous clamping of the common bile duct. To demonstrate the applicability of the technique, we injected either phosphate-buffered saline or dimethyl sulfoxide in concentrations of 50 or 65% and compared these groups with sham-operated mice. The surgery was optimized to achieve a mortality rate close to 0. There were no significant changes in pain, activity level, or mortality from the day of the surgery until euthanization for any groups. Injection of phosphate-buffered saline or 50% dimethyl sulfoxide was generally well-tolerated, whereas 65% dimethyl sulfoxide led to higher weight loss, an increase of serum alanine transaminase, and histological portal inflammation. There were no signs of inflammation in the gut. We have developed a bile duct injection technique that is well-tolerated, easily reproducible, and that may complement existing models of cholangiopathies. Direct access to the bile ducts without causing harm to the hepatobiliary or intestinal tissue may be valuable in future studies of normal biliary physiology and different pathophysiological mechanisms of disease and to test novel therapeutic strategies. NEW & NOTEWORTHY To evaluate tolerability of the bile duct to injection of both polar and nonpolar compounds, we established a novel biliary injection technique. This technique is well-tolerated, easily reproducible, and with direct access to the bile ducts for studies of the murine biliary tree. The bile duct injection technique may complement existing animal models and be a valuable tool in future studies of normal biliary physiology or pathophysiology and to test novel therapeutic strategies.

KEYWORDS:

animal models; biliary cirrhosis; cholangiocyte biology; cholangitis; cholestasis

PMID:
29212771
DOI:
10.1152/ajpgi.00124.2017
[Indexed for MEDLINE]
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