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 11 [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 portorsistemic collateral circulation, associated with mesenteric venous vasculopathy and increased plasma levels of bilinubin (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. (c) 2008 Wiley-Liss, Inc.