Header

UZH-Logo

Maintenance Infos

Characterization of time-related changes after experimental bile duct ligation


Georgiev, P; Jochum, W; Heinrich, S; Jang, J H; Nocito, A; Dahm, F; Clavien, P A (2008). Characterization of time-related changes after experimental bile duct ligation. British Journal of Surgery, 95(5):646-656.

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 alpha-smooth muscle actin-positive cells and the expression of transforming growth factor beta1, 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.

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 alpha-smooth muscle actin-positive cells and the expression of transforming growth factor beta1, 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.

Statistics

Citations

106 citations in Web of Science®
113 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:15 Dec 2008 14:00
Last Modified:05 Apr 2016 12:42
Publisher:Wiley-Blackwell
ISSN:0007-1323
Publisher DOI:https://doi.org/10.1002/bjs.6050
PubMed ID:18196571

Download

Full text not available from this repository.
View at publisher