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Characterization of time-related changes after experimental bile duct ligation

Authors

  • P. Georgiev,

    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
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  • W. Jochum,

    1. Department of Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • S. Heinrich,

    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
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  • J. H. Jang,

    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
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  • A. Nocito,

    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
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  • F. Dahm,

    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
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  • P.-A. Clavien

    Corresponding author
    1. Swiss Hepato-Pancreato-Biliary Centre, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland
    • Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
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  • Presented in part to the Annual Meeting of the Swiss Surgical Society, Lugano, Switzerland, June 2006

  • The Editors are satis.ed that all authors have contributed signi.cantly to this publication

Abstract

Background:

Although bile duct ligation (BDL) in mice is used to study cholestasis, a detailed description of this animal model is lacking. The aim of this study was to define specific phases of acute and chronic injury and repair in the different cellular compartments of the liver.

Methods:

C57BL/6 mice underwent BDL or sham laparotomy, and serum and liver tissue were analysed between 8 h and 6 weeks later.

Results:

Biliary infarcts and alanine aminotransferase levels revealed acute hepatocellular injury peaking at days 2–3, paralleled by enhanced transcription of pro-proliferative mediators and followed by a distinct peak of hepatocellular proliferation at day 5. Cholangiocellular proliferation occurred in large bile ducts on days 2–3 and in small bile ducts on day 5. Neutrophil infiltration occurred within 8 h, with neutrophils remaining the predominant immune cell type until day 3. Acute injury was followed by continuous tissue repair, lymphocyte and Kupffer cell infiltration, and accumulation of collagen during the second week. Thereafter, the number of α-smooth muscle actin-positive cells and the expression of transforming growth factor β1, tissue inhibitor of metalloproteinases 1 and procollagen (I) decreased, and liver fibrosis stabilized.

Conclusion:

BDL elicits dynamic changes in mouse liver. The chronological dissection and quantification of these events identified specific phases of acute and chronic cholestatic liver injury. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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