ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9
| Autor: | Xi-shan Yang, Ying Meng, Ling-Fei Mi, Xu Li, Shao-Xi Cai |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Platelet-derived growth factor Becaplermin CCL4 Angiotensin-Converting Enzyme Inhibitors Matrix metalloproteinase Matrix Metalloproteinase Inhibitors digestive system Transforming Growth Factor beta1 chemistry.chemical_compound Transforming Growth Factor beta Internal medicine medicine Animals cardiovascular diseases Rats Wistar Platelet-Derived Growth Factor biology Carbon Tetrachloride Poisoning Gastroenterology NF-kappa B NF-κB General Medicine Transforming growth factor beta Proto-Oncogene Proteins c-sis NFKB1 Rats Endocrinology Basic Research chemistry Perindopril biology.protein Cancer research Platelet-derived growth factor receptor Transforming growth factor |
| Zdroj: | World journal of gastroenterology. 11(31) |
| ISSN: | 1007-9327 |
| Popis: | 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.Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl(4) 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with 40% of CCl(4). 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 AT1R, TGF-beta1 and PDGF-BB were examined by Western blot. Nuclear factor kappaB (NF-kappaB) 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.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-beta1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-kappaB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-kappaB DNA binding activity.Perindopril attenuates CCl(4)-induced hepatic fibrogenesis of rat by inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9. |
| Databáze: | OpenAIRE |
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