Up-regulation of components of the renin-angiotensin system in liver fibrosis in the rat induced by CCL₄.

The purpose of this study was to investigate the components of renin-angiotensin system (RAS), liver function and histology in liver fibrogenesis in the rats induced by low-dose chronic carbon tetrachloride (CCL4) administration and evaluate the relationship between biochemical variables and components of RAS. Male Sprague-Dawley (SD) rats were randomly divided into the CCL4 group which received intraperitoneal injection of 40% CCL4 dissolved in olive oil every three days for four consecutive weeks (Initial dose was 5 mL/kg, other dose: 3 mL/kg) and the control group which received the same dose of olive oil. The micro-structure of the liver was examined by H&E. Hepatic Ang II and Ang(1-7) was detected. Real-time PCR and Western-blot were performed to determine the gene and protein expression of the RAS. The components of RAS were all up-regulated in CCL4 group, and the increased extent of ACE-Ang II-AT1 axis was higher than the ACE2-Ang(1-7)-Mas axis. There was a significant correlation between ACE and ACE2 gene expression, AT1 and MAS gene expression, Ang II and Ang(1-7) in the liver of rats. ACE (or ACE2) gene expression strongly correlated with the index of liver injury significantly. These results suggest hepatic fibrogenesis induced by chronic CCL4 administration may be associated with the relationship of ACE-Ang II-AT1 axis and ACE2-Ang(1-7)-MAS axis.