THE ROLE OF ENALAPRIL IN PATHOGENESIS OF CCL4 INDUCED HEPATIC FIBROSIS

Objective The present study was designed to examine whether the renin-angiotensin system would be implicated in the development of hepatic fibrosis induced by CCI4. The effects of enalapril on the ex-pression of platelet derived growth factor receptor (PDGFR) in liver tissue were also investigated. Methods 50 Sprague-Dawley rats were randomly divided into S groups (control group, model group, and 3 enalapril treated groups). Except rats of the model group, all rats received subcutanous injection of 40% CC14 (every 3d for 6 weeks). Rats of enalapril treated groups were given enalapril (10mg/kg, 5mg/kg, 2.5mg/kg per day, orally)for 6 weeks before they were killed. Serum levels of hyaluronic acid (HA) and laminin (LW) were de-termined by radioimmunoassay techniques. Van Gieson collagen staining was used to evaluate the extracellular matrix of the liver. The expressions of PDGFR and a-smooth muscle actin (a-SMA) were confirmed by im-munohistochemical methods. Results Compared with those in the model gr oup, it was found in enalapril treated groups: (1) serum levels of collagen type 1V and LN were significantly reduced (P< 0. 01); (2) the pro-gression of fibrosis was delayed (P < 0. 01); (3) the expressions of PDGFR and a-SMA were decreased. Conclusion The renin-angiotensin system was involved in the development of hepatic fibrosis induced by Cd4. Angiotensin-converting enzyme (ACE) inhibitor and enalapril could slow down the rate of hepatic fibrosis. This effect might be due to the ability of this drug in suppressing the expression of PDGFR of liver tissue.