Intrahepatic biliary ablation with pure ethanol: an experimental model of biliary atresia.
OBJECTIVE
We describe a new rat model of biliary atresia, induced by biliary ablation with pure ethanol.


METHODS
A catheter was inserted and fixed in the common bile duct of male rats. Saline or pure ethanol was injected through the catheter and the animals were monitored for 8 weeks thereafter. We measured total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid (HA) and examined liver biopsy specimens immunohistochemically for α-smooth muscle actin staining (α-SMA) and transforming growth factor-β1 (TGF-β1).


RESULTS
The ethanol injection group animals were further divided into a temporary and a persistent liver dysfunction group. In the persistent group, T-Bil, AST, ALT and HA levels were significantly higher after 8 weeks in the persistent group than in the control group and the temporary group. In the ethanol injection group, α-SMA expression was prominent in the surrounding proliferative bile ducts and portal areas. The distribution of TGF-β1 was found prominently in hepatocytes in the center of nodules and in ductular epithelial cells.


CONCLUSIONS
This study characterizes the effects of ethanol-induced bile duct injury in rats, resulting in sclerosing cholangitis and its secondary effects. We believe that this experimental model will prove useful in the study of biliary atresia.
Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara Cho, Sakyo-ku, Kyoto 606-8507, Japan. tatekawa3966@diary.ocn.ne.jp
Yukihiro
Y
Tatekawa
Akira
A
Nakada
Tatsuo
T
Nakamura
D000199:Actins / Q000378:metabolism; D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D001656:Biliary Atresia / Q000139:chemically induced* / Q000473:pathology / Q000601:surgery; D015209:Cholangitis, Sclerosing / Q000139:chemically induced; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D000431:Ethanol; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat