Surgical Technique| Volume 149, ISSUE 3, P445-451, March 2011

Partial bile duct ligation in mice: A novel model of acute cholestasis

Published:September 06, 2010DOI:


      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.


      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.


      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.


      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Clavien P.A.
        • Petrowsky H.
        • DeOliveira M.L.
        • Graf R.
        Strategies for safer liver surgery and partial liver transplantation.
        N Engl J Med. 2007; 356: 1545-1559
        • Schroeder R.A.
        • Marroquin C.E.
        • Bute B.P.
        • Khuri S.
        • Henderson W.G.
        • Kuo P.C.
        Predictive indices of morbidity and mortality after liver resection.
        Ann Surg. 2006; 243: 373-379
        • Li M.K.
        • Crawford J.M.
        The pathology of cholestasis.
        Semin Liver Dis. 2004; 24: 21-42
        • Johnstone J.M.
        • Lee E.G.
        A quantitative assessment of the structural changes the rat’s liver following obstruction of the common bile duct.
        Br J Exp Pathol. 1976; 57: 85-94
        • Georgiev P.
        • Jochum W.
        • Heinrich S.
        • Jang J.H.
        • Nocito A.
        • Dahm F.
        • et al.
        Characterization of time-related changes after experimental bile duct ligation.
        Br J Surg. 2008; 95: 646-656
        • Fickert P.
        • Zollner G.
        • Fuchsbichler A.
        • Stumptner C.
        • Weiglein A.H.
        • Lammert F.
        • et al.
        Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles.
        Gastroenterology. 2002; 123: 1238-1251
        • Burkard I.
        • von Eckardstein A.
        • Rentsch K.M.
        Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry.
        J Chromatogr. 2005; 826: 147-159
        • Wiener S.M.
        • Hoyt Jr., R.F.
        • Deleonardis J.R.
        • Clevenger R.R.
        • Jeffries K.R.
        • Nagashima K.
        • et al.
        Manometric changes during retrograde biliary infusion in mice.
        Am J Physiol Gastrointest Liver Physiol. 2000; 279: G49-G66
        • Setchell K.D.
        • Rodrigues C.M.
        • Clerici C.
        • Solinas A.
        • Morelli A.
        • Gartung C.
        • et al.
        Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei.
        Gastroenterology. 1997; 112: 226-235
        • Hoekstra H.
        • Tian Y.
        • Jochum W.
        • Stieger B.
        • Graf R.
        • Porte R.J.
        • et al.
        Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression.
        Transplantation. 2008; 85: 1159-1166
        • Fickert P.
        • Fuchsbichler A.
        • Wagner M.
        • Zollner G.
        • Kaser A.
        • Tilg H.
        • et al.
        Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice.
        Gastroenterology. 2004; 127: 261-274
        • Lazaridis K.N.
        • Strazzabosco M.
        • Larusso N.F.
        The cholangiopathies: disorders of biliary epithelia.
        Gastroenterology. 2004; 127: 1565-1577
        • Feliu J.
        • Mel R.
        • Borrega P.
        • Lopez Gomez L.
        • Escudero P.
        • Dorta J.
        • et al.
        Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas.
        Ann Oncol. 2002; 13: 1756-1762
        • Corrie P.
        • Mayer A.
        • Shaw J.
        • D’Ath S.
        • Blagden S.
        • Blesing C.
        • et al.
        Phase II study to evaluate combining gemcitabine with flutamide in advanced pancreatic cancer patients.
        Br J Cancer. 2002; 87: 716-719
        • Kosuge T.
        • Yamamoto J.
        • Shimada K.
        • Yamasaki S.
        • Makuuchi M.
        Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection.
        Ann Surg. 1999; 230: 663-671
        • Sewnath M.E.
        • Karsten T.M.
        • Prins M.H.
        • Rauws E.J.
        • Obertop H.
        • Gouma D.J.
        A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice.
        Ann Surg. 2002; 236: 17-27