2.4. Surgery-based Animal model
2.4.1. Common bile duct ligation: In this model, hepatic cirrhosis is induced by surgically ligating the bile duct. As rats lack gallbladder, they are better suited for this technique. Once the bile duct is ligated in rats, there is cholestatic injury, inflammation and progression to liver cirrhosis. Initially, laparotomy to the mid-ventral region is performed in the rodent. First ligation is done in the pancreatic duct and second ligation is done at the junction present below the hepatic duct. The gap between the ligations of the bile duct is to prevent perforation (98). After this procedure, hepatic cirrhosis is developed within 21-28 days. It results in inflammation, release of cytokines and enhanced biliary pressure due to blockage of the bile duct. There is a rise in the release of fibrosis causing mediators like collagen 1 and metalloproteinases inhibitors. It triggers the release of free radicals and B cells, T cell accumulation in the hepato-portal tract. Interleukins and prostaglandins are stimulated, leading to commence inflammatory response resulting in hepatic cirrhosis (99).
2.4.2. Obliterative micro sx: Obliterative micro sx is a microsurgical technique, an alternative to common bile duct ligation. This technique involves a section of the extrahepatic biliary tract that joins to CBD and drains all the liver lobes. After a month post-surgery, abscesses form in the hepatopulmonary region and affect the levels of bilirubin, bile acids, gamma-glutamyl transpeptidase and alkaline phosphatase. This technique is valid for the study of obstructive jaundice and extrahepatic biliary artesia (100, 101).
2.4.3. Transplantation: Bile duct allografts were made via ligation of bile duct at different ages of mice i.e. fetal (at day 18), postnatal (at day 21) and adult (at 6 weeks) were ligated. This leads to hepatocellular injury. Histopathological changes and luminal architecture can be evaluated after a week of grafting. The primary sclerosing cholangitis can be analysed after 3 weeks through transplantation in subcapsular allograft knockout C57BL/6 and B1O.A mice (102).
2.4.4. Organ culture: An organ culture model includes combining periportal mesenchyme with a liver fragment of the 15-day-old embryo of a rodent. Mesenchymal invasion in regards to cluster, rosette or vesicle formation is evaluated. The porta hepatis is the fissure on the visceral surface of the liver where major vessels and ducts enter or leave the liver. Differentiation of mesenchymal cells to hepatocytes forming intrahepatic lining and fusion of extra- and intra-hepatic lining in later stages of porta hepatis development is evaluated (103).