A Useful Model to Audit Liver Resolution from Cirrhosis in Rats Using Functional Proteomics

Background: We conducted a rat cirrhosis and recovery model, on the basis of which proteomics was used to audit liver resolution from cirrhosis. Materials and methods: Micronodular cirrhosis was established using Sprague-Dawley rats fed thioacetamide, and spontaneous recovery from cirrhosis was acquired after thioacetamide withdrawal. Results: Over the course of a 2-, 3-, and 6-week recovery, macronodular cirrhosis, uneven liver surface, and nearly normal liver surface were acquired, respectively. Specific liver enzymes, hepatitis activity index, hepatocytes apoptosis index, number of activated Kupffer cells and hepatic stellate cells, and area of fibrosis bands consistently peaked at the end of thioacetamide administration and decreased progressively during the recovery period. mRNA expression of proinflammatory cytokines and proapoptotic molecules peaked around the end of thioacetamide administration and decreased thereafter. Using two-dimensional gel electrophoresis, the seven most upregulated and six most downregulated protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight. Of these, GST-P2 and its isoforms, GST-α and GST-M, were chosen for further validation using immunohistochemistry. Expression of GST-P peaked at the 2-week recovery, whereas GST-α and GST-M remained at strong levels at the 6-week recovery. Conclusions: The mechanism of resolution from cirrhosis can be extensively investigated using the presented model which, for example, showed GST isoforms performing their roles at different time phases.