Korean J Hepatol > Volume 13(1); 2007 > Article
The Korean Journal of Hepatology 2007;13(1): 61-69.
Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-Ligated Rats
Dong Hun Park, M.D., Soon Koo Baik, M.D., Yeon Hee Choi, Moon Young Kim, M.D., Dae Wook Rhim, M.D., Jae Woo Kim, M.D., Sang Ok Kwon, M.D., Mi Yun Cho, M.D.1, Chul Han Kim, M.D.2, and Seung Chan Ahn, M.D.3
Department of Internal Medicine, 1Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea; 2Andong General Hospital, 3Dr. Ahn's Internal Medicine Clinic
s 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
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