Development of an experimental model of cholestasis induced by hypoxic/ischemic damage to the bile duct and liver tissues in infantile rats

• Published in: Journal of gastroenterology 2011-05, Vol.46 (5), p.639-647
• Main Authors: Toki, Fumiaki, Takahashi, Atsushi, Suzuki, Makoto, Ootake, Sayaka, Hirato, Junko, Kuwano, Hiroyuki
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Age Factors; Animals; Animals, Newborn; Asphyxia neonatorum; Bile Ducts - blood supply; Bile Ducts - pathology; Bile Ducts, Extrahepatic - blood supply; Bile Ducts, Extrahepatic - pathology; Biliary Tract; Cholestasis; Cholestasis - physiopathology; Colorectal Surgery; Disease Models, Animal; Fibrosis - pathology; Gastroenterology; Hepatology; Hypoxia - complications; Ischemia; Ischemia - complications; Jaundice, Obstructive; Liver; Liver - blood supply; Liver - pathology; Liver Function Tests; Medicine; Medicine & Public Health; Original Article—Liver; Pancreas; Povidone; Rats; Rats, Wistar; Surgical Oncology
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-010-0330-5

Background We aimed to develop experimental models of hypoxia/ischemia-induced cholestasis using neonatal and infantile rats. Methods Hypoxia/ischemia was induced in the bile duct (BD) by injecting prostaglandin (PG) at birth and/or by coagulation of the hepatic artery (CHA) at about 3 weeks after birth. The rats were divided into 6 groups: control; PG-injected; sham-operated with or without PG; CHA; and CHA + PG. CHA was also performed in adult rats. Liver specimens and blood samples were obtained at 5 weeks after birth, and immunohistochemical and biochemical examinations were performed. Results (1) BD proliferation with fibrosis (BDPF) was found in the intrahepatic portal tract in the CHA and CHA + PG groups. Low-grade BDPF was observed in the PG group. (2) Cyst formation in the extrahepatic BD (EBD) was observed in the porta hepatis of some rats in the CHA and CHA + PG groups. In these groups, the number of peribiliary vascular plexuses (PVPs) decreased. BD proliferation and infiltration of inflammatory cells were observed in the EBD wall in the CHA + PG group. (3) Ki-67 was expressed in BD and EBD cells in the CHA + PG group. (4) BDPF was not detected in adult rats with CHA. (5) Serum liver function tests indicated obstructive changes in the EBD in the CHA and CHA + PG groups. Conclusion Reduced blood flow in the EBD during infancy induced BDPF and obstructive changes in the EBD, which may, along with immature PVP and inflammatory changes in the EBD, contribute to hypoxia/ischemia of the EBD.