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Korean J Hepatol. 2007;13(1):61-69. Published online January 1, 1970.
- Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-Ligated Rats
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- Abstract
- Backgrounds
and Aims: Angiotensin receptors are found on hepatic stellate cells, which participate in
hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study
was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model.
Material and methods: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL)
in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL
without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100
mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks
following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth
muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and
expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. Results: Batts & Ludwig
score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was
significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively
(p<0.05). The concentration of hydroxyproline (μg/g liver tissue) was lower in G3 and G4 compared with G1
(p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression
of collagen, procollagen, and TGF-beta mRNA. Conclusions: Angiotensin blockades are effective in the
prevention of hepatic fibrosis in BDL rats. (Korean J Hepatol 2007;13:61-69)
Keywords :Fibrosis; Angiotensin-converting enzyme inhibitors; Angiotensin II type I receptor blockers; Liver; Rats
