Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis.
- Author:
Zi-Yu DENG
1
;
Jun LI
;
Yong JIN
;
Xiao-Liang CHEN
;
Xiong-Wen LÜ
Author Information
- Publication Type:Journal Article
- MeSH: Actins; metabolism; Alkaloids; pharmacology; Animals; Anti-Arrhythmia Agents; pharmacology; Carbon Tetrachloride; Collagen; metabolism; Collagen Type IV; metabolism; Hyaluronic Acid; metabolism; Hydroxyproline; metabolism; Laminin; metabolism; Liver Cirrhosis; chemically induced; drug therapy; metabolism; Male; Procollagen; metabolism; Quinolizines; pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects; p38 Mitogen-Activated Protein Kinases; metabolism
- From: Chinese Medical Journal 2009;122(12):1449-1454
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDRecent studies have suggested that p38 mitogen-activated protein kinases (MAPK) signalling pathway plays an important role in hepatic fibrosis. This study explored the antifibrotic effect of oxymatrine on tetrachloromethane induced liver fibrosis in rats and its modulation on the p38 MAPK signalling pathway.
METHODSOne hundred and twenty healthy male Sprague-Dawley rats were randomly assigned to six groups: normal (n = 20), induced fibrosis (n = 20), colchicine (n = 20) and three treatment groups of oxymatrine (n = 20 x 3). We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), procollagen III (PCIII) and hydroxyproline (Hyp), a-smooth muscle actin (alpha-SMA) and phosphor-p38 (pp38).
RESULTSThe relative indicators of changes in histopathology, HA, LN, CIV, PCIII, Hyp, alpha-SMA and pp38 were raised significantly in the induced fibrosis group (P < 0.01 vs normal group). The semiquantitative hepatic fibrosis staging scores of middle dose group and high dose group were decreased (P < 0.05 and P < 0.01 respectively vs the induced fibrosis group), as was the average area of collagen in rats' liver, the concentrations of serum HA, LN, CIV, PCIII and liver tissue homogenate Hyp. The gene expression of alpha-SMA mRNA was considerably decreased in the treated animals, as was the protein espression of pp38 protein.
CONCLUSIONSOxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats in ways which relate to modulating the fibrogenic signal transduction via p38 MAPK signalling pathway.