Biliary fibrosis in microsurgical extrahepatic cholestasis in the rat.
A new model of extrahepatic cholestasis, using a microsurgical technique, is performed as an alternative to the traditional model of the bile duct ligated-rat, in order to study the stage of fibrosis in the long-term. Male Wistar rats were divided into two groups: I (Sham-operated, n = 9) and II [Microsurgical Cholestasis (MC), n = 10]. After 4 weeks, portal pressure, types of portosystemic collateral circulation, mesenteric venous vasculopathy, hepatic function test, and liver histopathology were studied by using the Knodell index and fibrosis was determined by reticulin and Sirius red stains. The animals with MC presented portal hypertension with extrahepatic portosistemic collateral circulation, associated with mesenteric venous vasculopathy and increased plasma levels of bilirubin (6.30 +/- 1.80 vs. 0.22 +/- 0.37 mg/dL; P = 0.0001), alkaline phosphatase (293.00 +/- 82.40 vs. 126.30 +/- 33.42 U/L; P = 0.001), AST (380.00 +/- 78.50 vs. 68.33 +/- 11.74 IU/L; P = 0.0001), ALT (87.60 +/- 22.32 vs. 42.22 +/- 7.89 IU/L; P = 0.0001), and LDH (697.76 +/- 75.13 vs. 384.80 +/- 100.03 IU/L; P = 0.0001). On the contrary, plasma levels of albumin decreased (2.72 +/- 0.12 mg/dl vs. 2.99 +/- 0.10; P = 0.001). The microsurgical resection of the extrahepatic biliary tract in the rat produces an experimental model of hepatic inflammation, characterized by a high Knodell hepatic activity index (4), bile proliferation, and fibrosis.
Department of Surgery, School of Medicine, Complutense University, Madrid, Spain.
Fernando
F
Sánchez-Patán
Raquel
R
Anchuelo
María-Teresa
MT
Corcuera
Isabel
I
Casado
Fernando
F
Gómez-Aguado
María-Angeles
MA
Aller
Arturo
A
Cruz
María-José
MJ
Alonso
Jaime
J
Arias
D000818:Animals; D017734:Bile Ducts, Extrahepatic / Q000473:pathology* / Q000601:surgery*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001651:Cholestasis, Extrahepatic / Q000503:physiopathology*; D004195:Disease Models, Animal; D005355:Fibrosis; D008107:Liver Diseases / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008866:Microsurgery / Q000379:methods*; D009929:Organ Size; D017082:Portal Pressure; D051381:Rats; D017208:Rats, Wistar