Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis.
OBJECTIVE
To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis.


METHODS
Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining).


RESULTS
Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations.


CONCLUSIONS
We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.
Prado
Ivete Bedin
IB
Hospital das Clínicas, Faculty of Medicine, University of São Paulo, Brazil.
dos Santos
Marília Harumi Higuchi
MH
Lopasso
Fábio Pinatel
FP
Iriya
Kiyoshi
K
Laudanna
Antonio Atílio
AA
D000210:Acute-Phase Reaction; D000818:Animals; D001652:Bile Ducts / Q000473:pathology* / Q000601:surgery; D002779:Cholestasis / Q000473:pathology*; D004108:Dilatation, Pathologic / Q000473:pathology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000473:pathology*; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis