Published online Aug 15, 2000. doi: 10.3748/wjg.v6.i4.540
Revised: February 22, 2000
Accepted: March 4, 2000
Published online: August 15, 2000
AIM: To investigate effect o f losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl4; and to determine whether or not AT1 receptors are expressed on hepatic stellate cells.
METHODS AND RESULTS: Fifty male Sprague-Dawley rats, weighing (180 ± 20) g, were randomized into five groups (control group, model group, and three los artan treated groups), in which all rats were given the subcutaneous injection o f 40% CCl4 (every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-β), and alpha-smooth muscle actin (α-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (t = 4. 20, P < 0.01 and t = 4.57, P < 0.01). Serum HA and PC III also had significant differences (t = 3.53, P < 0.01 and t = 2.20, P < 0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-β, and α-SMA in liver tissue.
CONCLUSION: AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl4. The mechanism may be relat ed to the decrease in the expression of AT1 receptors and TGF-β, a meliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.