Selective biliary occlusion in rodents: Description of a new technique

Abstract

Background: Modern therapy concepts are of limited success in patients with cholestasis (e.g., biliary occluding malignancies). Therefore, we established a new animal model enabling simultaneous investigation of liver regeneration and hepato-biliary remodelling in biliary obstructed and biliary non-obstructed liver lobes. Methods: Biliary occlusion of different extent was induced in 50 male rats: Ligation and transection of the common bile duct (100% of liver, tBDT, n=25); or of the left bile duct (70% of liver, sBDT, n=25). At postoperative days 1, 3, 7, 14 and 28 we assessed the hepatic histomorphological alterations, proliferative repair, progress of liver fibrosis (HE, BrdU, EvG) and signs of liver regeneration (liver lobe weight gain). In addition, we determined systemic markers of hepatocellular injury (ASAT, ALAT), cholestasis (Bilirubin) and synthetic liver function (INR). The animals were monitored daily (body weight gain, stress score, survival). Results: All animals survived until the planned date of sacrifice. sBDT induced in the biliary occluded liver lobes similar histomorphological alterations, proliferative repair and progress of liver fibrosis like tBDT. In the biliary non-ligated liver lobes in sBDT animals we noticed a temporarily enhanced biliary proliferation and a persistent low grade liver fibrosis in the periportal area. Conclusions: Our model of sBDT represents a safe and valid method to induce selective cholestasis. The model enables further comparative investigation of liver regeneration in different extents of occlusive cholestasis (e.g., mimicking biliary occluding malignancies).