Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-ligated Rats.
- Author:
Dong Hun PARK
1
;
Soon Koo BAIK
;
Yeon Hee CHOI
;
Moon Young KIM
;
Dae Wook RHIM
;
Jae Woo KIM
;
Sang Ok KWON
;
Mi Yun CHO
;
Chul Han KIM
;
Seung Chan AHN
Author Information
1. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. baiksk@yonsei.ac.kr
- Publication Type:Original Article ; English Abstract
- Keywords:
Fibrosis;
Angiotensin-converting enzyme inhibitors;
Angiotensin II type I receptor blockers;
Liver;
Rats
- MeSH:
Actins/metabolism;
Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use;
Animals;
Bile Ducts/pathology/surgery;
Captopril/administration & dosage/*therapeutic use;
Fibrosis;
Hydroxyproline/metabolism;
Ligation;
Liver/drug effects/metabolism/pathology;
Liver Cirrhosis, Experimental/*drug therapy/etiology/metabolism;
Losartan/administration & dosage/*therapeutic use;
Male;
Rats;
Rats, Sprague-Dawley;
Transforming Growth Factor beta/metabolism
- From:The Korean Journal of Hepatology
2007;13(1):61-69
- CountryRepublic of Korea
- Language:Korean
-
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 (microgram/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.
