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KMID : 1103920070130010061
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Korean Journal of Hepatology
2007 Volume.13 No. 1 p.61 ~ p.69
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Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-Ligated Rats
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Park Dong-Hun
Baik Soon-Koo
Choi Yeon-Hee
Kim Moon-Young
Rhim Dae-Wook
Kim Jae-Woo
Kwon Sang-Ok
Cho Mee-Yon
Kim Chul-Han
Ahn Seung Chan
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Abstract
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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.
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KEYWORD
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Fibrosis, Angiotensin-converting enzyme inhibitors, Angiotensin 2 type 1 receptor blockers, Liver, Rats
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