ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

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 fibrosi...

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Published in:World journal of gastroenterology : WJG 2005-08, Vol.11 (31), p.4807-4811
Main Author: Li, Xu
Format: Article
Language:English
Subjects:
Basic Research
TGF-β1
四氯化碳
核因子-κB
肝纤维化
血管紧缩素转化酶抑制剂
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Summary: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·d）, 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 ATIR, 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 ATIR in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of ATIR, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA bindingactivity 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-BB and MMP-2,9.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v11.i31.4807