Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2005; 11(31): 4807-4811
Published online Aug 21, 2005. doi: 10.3748/wjg.v11.i31.4807
ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9
Xu Li, Ying Meng, Xi-Shan Yang, Ling-Fei Mi, Shao-Xi Cai
Xu Li, Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Ying Meng, Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Xi-Shan Yang, Department of Digestive Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Ling-Fei Mi, Department of Emergency, the First People’s Hospital of Huaihua 418000, Hunan Province, China
Shao-Xi Cai, Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of China, No.30270610
Correspondence to: Dr. Xu Li, Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China. mylx99@163.com
Received: October 23, 2004
Revised: December 23, 2004
Accepted: December 26, 2004
Published online: August 21, 2005
Abstract

AIM: Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis.

METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with 40% of CCl4. Perindopril, equivalent to 2 mg/(kg昫), was administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9 (MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.

RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.

CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

Keywords: Renin-angiotensin-aldosterone system; Angiotensin-converting enzyme inhibitor; Hepatic fibrosis