Background
The standard model for research in cholestasis is the total ligation of the bile duct
(tBDL). Because this model causes severe hepatic injury in mice, we developed a novel
model of cholestasis using a partial bile duct ligation (pBDL) and evaluate different
mechanisms of injury.
Methods
Male C57Bl/6 mice were subjected to sham operation, tBDL, or pBDL. Blood from tail
veins was taken repeatedly until day 14 after surgery to assess markers of tissue
injury (aspartate aminotransferase [AST]) and cholestasis (bilirubin, alkaline phosphatase
[AP]). Also, liver samples were obtained at various time points to determine the histologic
injury (hematoxylin and eosin) and tissue repair (Ki67). In addition, the biliary
pressure and serum bile acids were evaluated as potential mechanisms of injury.
Results
Both models of cholestasis were equal in terms of bilirubin, AST, and AP serum levels
during the first week of the experiment. Although these parameters remained constantly
elevated thereafter in the tBDL model, all parameters normalized within the second
week after pBDL. Moreover, pBDL resulted in significantly less necrosis formation
(P = .001) and consequent hepatocyte proliferation (P = .01). Most important, serum bile acid levels (P = .04) and biliary pressures (P = .02) were significantly lower after pBDL than after tBDL and were the best predictors
for hepatic necrosis formation.
Conclusion
We established a model of acute cholestasis, which is ideal for research in resolved
acute cholestasis (eg, surgery for Klatskin tumors). Moreover, biliary pressure and
toxic bile acid serum levels may be better predictors of cholestatic liver injury
than standard laboratory parameters.
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Article info
Publication history
Published online: September 06, 2010
Accepted:
July 22,
2010
Identification
Copyright
© 2011 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
