Biliary fibrosis in microsurgical extrahepatic cholestasis in the rat

Abstract

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.

A half century (1961-2011) of applying microsurgery to experimental liver research

“…An advantage of the microsurgical technique of extrahepatic cholestasis in the rat is the absence of biliary pseudocyst formation, hepatopulmonary infection, and thus the prevention of mortality related to sepsis [22,23] . In rats with microsurgical extrahepatic cholestasis, the weekly administration of antibiotics and vitamin K allows rodents to survive for more than 8 wk [24,25] . In the long-term evolution, both macrosurgical (BDL) and microsurgical experimental cholestasis models develop hepatomegaly with a marked ductular proliferation and fibrosis, but the loss of normal liver architecture, typical of cirrhosis, is seldom found [24][25][26] .…”

“…In rats with microsurgical extrahepatic cholestasis, the weekly administration of antibiotics and vitamin K allows rodents to survive for more than 8 wk [24,25] . In the long-term evolution, both macrosurgical (BDL) and microsurgical experimental cholestasis models develop hepatomegaly with a marked ductular proliferation and fibrosis, but the loss of normal liver architecture, typical of cirrhosis, is seldom found [24][25][26] . In relation to extrahepatic alterations, jaundice, choluria, PH with enlarged spleen and collateral portosystemic circulation, hepatic encephalopathy and ascites, stand out [25,27] .…”

Effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus in rats

“…In this study, 36 rats were used and divided into 9 groups (n = 4 per group). BDL rats were prepared using a previously reported method with some modifications [17]. The animals were anesthetized with an intraperitoneal injection of sodium pentobarbital (32 mg/kg body weight), and BDL was performed through flank incisions; subsequently, the muscle layers and the skin were sutured to close the wound.…”

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

“…In the long-term evolution, between 8 to 10 weeks, microsurgical extrahepatic cholestatic-rats develop hepatomegaly with a marked ductular proliferation and fibrosis [150]. It has been suggested that liver fibrogenesis resembles a wound-healing process leading to scar formation [151][152][153].…”