HEPATIC INFLAMMATION: ANIMAL MODELS
Regulation of the cell cycle and the apoptosis techniques used Real Time PCR, ELISA, Western Blot, Immunocytochemistry. In vivo studies inflammation: hepatitis induced by chemical agent. The acute carbon tetrachloride (CCl4) intoxication is the widely used model of hepatitis. It is able to induce acute inflammation. Concanavaline (ConA) is able to induce a rapid and reliable hepatitis mediated by lymphocytes.
Similarities with the human autoimmune hepatitis
This model shares some similarities with the human autoimmune hepatitis. In bile-induced hepatitis, ligation of the extrahepatic bile duct leads to an acute hepatitis. Inflammation is evaluated using histology, plasma level of transaminases, and liver expression of mediators of inflammation (cytokines). Fibrosis chronic exposition to CCl4 leads to an important liver fibrosis. Fibrosis is graded using specific staining of liver histological specimens (sirus red, METAVIR scoring), hydroxyproline content, quantification of fibrogenic mediators (SMA, collagen, TGF).
Liver regeneration: The two-thirds partial hepatectomy in mice is a reliable model to study the effects of compounds on liver regeneration. Hepatocyte regeneration could also be evaluated after acute CCl4 intoxication. In both models, liver regeneration is evaluated using macroscopic (liver weight gain) and histological (mitotic index and BrdU index) parameters. Liver levels of protein involved in acute phase (TNF, IL-6) and cell cycle (cyclin D1, c-myc) are quantified.
Which model to choose?
Based on our expertise, we will propose the most relevant animal model to evaluate the therapeutic properties of tested compounds.