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).