Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats

Dong Hun Park, Soonkoo Baik, Yeon Hee Choi, Moonyoung Kim, Dae Wook Rhim, Jae Woo Kim, Sang Ok Kwon, Meeyon Cho, Chul Han Kim, Seung Chan Ahn

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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 (microg/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.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalThe Korean journal of hepatology
Volume13
Issue number1
Publication statusPublished - 2007 Jan 1

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Angiotensins
Common Bile Duct
Bile Ducts
Ligation
Fibrosis
Liver
Procollagen
Captopril
Hydroxyproline
Transforming Growth Factor beta
Collagen
Hepatic Stellate Cells
Angiotensin Receptors
Losartan
Spectrophotometry
Portal Hypertension
Smooth Muscle
Sprague Dawley Rats
Actins
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Park, Dong Hun ; Baik, Soonkoo ; Choi, Yeon Hee ; Kim, Moonyoung ; Rhim, Dae Wook ; Kim, Jae Woo ; Kwon, Sang Ok ; Cho, Meeyon ; Kim, Chul Han ; Ahn, Seung Chan. / Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats. In: The Korean journal of hepatology. 2007 ; Vol. 13, No. 1. pp. 61-69.
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title = "Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats",
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 (microg/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.",
author = "Park, {Dong Hun} and Soonkoo Baik and Choi, {Yeon Hee} and Moonyoung Kim and Rhim, {Dae Wook} and Kim, {Jae Woo} and Kwon, {Sang Ok} and Meeyon Cho and Kim, {Chul Han} and Ahn, {Seung Chan}",
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Park, DH, Baik, S, Choi, YH, Kim, M, Rhim, DW, Kim, JW, Kwon, SO, Cho, M, Kim, CH & Ahn, SC 2007, 'Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats', The Korean journal of hepatology, vol. 13, no. 1, pp. 61-69.

Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats. / Park, Dong Hun; Baik, Soonkoo; Choi, Yeon Hee; Kim, Moonyoung; Rhim, Dae Wook; Kim, Jae Woo; Kwon, Sang Ok; Cho, Meeyon; Kim, Chul Han; Ahn, Seung Chan.

In: The Korean journal of hepatology, Vol. 13, No. 1, 01.01.2007, p. 61-69.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats

AU - Park, Dong Hun

AU - Baik, Soonkoo

AU - Choi, Yeon Hee

AU - Kim, Moonyoung

AU - Rhim, Dae Wook

AU - Kim, Jae Woo

AU - Kwon, Sang Ok

AU - Cho, Meeyon

AU - Kim, Chul Han

AU - Ahn, Seung Chan

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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 (microg/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.

AB - 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 (microg/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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