Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis

AIM： To explore the anti-fibrotic effect of Oxymatrine on CCl4-induced liver fibrosis in rats and its modulation on the TGFbeta-Smad signaling pathway. METHODS： One hundred healthy male SD rats were randomly divided into three groups： normal group （n = 20）, treatment group of Oxymatrine （n = 40） and...

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Published in:World journal of gastroenterology : WJG 2008-04, Vol.14 (13), p.2100-2105
Main Authors: Wu, Xiao-Ling, Zeng, Wei-Zheng, Jiang, Ming-De, Qin, Jian-Ping, Xu, Hui
Format: Article
Language:English
Subjects:
Alkaloids - pharmacology
Animals
Antiviral Agents - pharmacology
Carbon Tetrachloride - adverse effects
CREB-Binding Protein - metabolism
Liver Cirrhosis - pathology
Male
Models, Biological
Quinolizines - pharmacology
Rapid Communication
Rats
Rats, Sprague-Dawley
RNA, Messenger - metabolism
Smad Proteins - metabolism
Smad3 Protein - metabolism
Smad7 Protein - metabolism
TGF
Transforming Growth Factor beta - metabolism
四氯化碳
氧化苦参碱
肝纤维化
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Summary:AIM： To explore the anti-fibrotic effect of Oxymatrine on CCl4-induced liver fibrosis in rats and its modulation on the TGFbeta-Smad signaling pathway. METHODS： One hundred healthy male SD rats were randomly divided into three groups： normal group （n = 20）, treatment group of Oxymatrine （n = 40） and CCh-induced fibrosis group （n = 40）. Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCh soluted in liquid paraffin with the concentration of 300 g/L, the dosage of injection was 3 mL/kg, twice per week for 8 wk）. The treated rats received Oxymatrine via celiac injection at a dosage of 10 mg/kg twice a week at the same time. The deposition of collagen was observed with H＆E and Masson staining. The concentration of serum TGF-β1 was assayed with ELISA. The gene expression of Smads and CBP （CREB binding protein） was detected with in situ hybridization （ISH） and immunohistochemistry （IH）, respectively. All the experimental figures were scanned and analyzed with special figure-analysis software. RESULTS： A significant reduction of collagen deposition and rearrangement of the parenchyma was noted in the liver tissue of Oxymatrine-treated rats. The semi- quantitative histological scores （2.43 ± 0.47 μm^2 vs 3.76 ±0.68, P 〈 0.05） and average area of collagen/in those rats were significantly decreased when compared with hepatic cirrhosis model rats （94.41 ± 37.26 μm^2 vs 290.86 ± 89.37 μm^2, P 〈 0.05）. The gene expression of Smad 3 mRNA was considerably decreased in the treated animals. The A value of Smad 3 mRNA was lower in the treated rats than the model rats （0.034 ± 0.090 vs 0.167 ± 0.092, P 〈 0.05）. Contrarily, the A value of Smad 7 mRNA was increased considerably in the treated animals （0.175 ± 0.065 vs 0.074 vs 0.012, P 〈 0.05）. There was an obvious decrease in the expression of CBP mRNA in treated rats as illuminated by a reduction of its A value when compared with model rats （0.065±0.049 vs 0.235 ± 0.025, P 〈 0.001）. CONCLUSION： Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats. Oxymatrine could promote the expression of Smad 7 and inhibit the expression of Smad 3 and CBP in CCh-induced hepatic fibrosis in SD rats, could modulate the fibrogenic signal transduction of TGFβ-Smad pathway.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.14.2100