Document Detail


Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis.
MedLine Citation:
PMID:  18395914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 CCl4-induced fibrosis group (n = 40). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4 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-beta1 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 semiquantitative histological scores (2.43 +/- 0.47 microm2 vs 3.76 +/- 0.68 microm2, 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 microm2 vs 290.86 +/- 89.37 microm2, 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 +/- 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 CCl4-induced hepatic fibrosis in SD rats, could modulate the fibrogenic signal transduction of TGFbeta-Smad pathway.
Authors:
Xiao-Ling Wu; Wei-Zheng Zeng; Ming-De Jiang; Jian-Ping Qin; Hui Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  14     ISSN:  1007-9327     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-08     Completed Date:  2008-07-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  2100-5     Citation Subset:  IM    
Affiliation:
Department of Digestion, General Hospital of Chengdu Military Command, Chengdu 610083, Sichuan Province, China.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / pharmacology*
Animals
Antiviral Agents / pharmacology
CREB-Binding Protein / metabolism
Carbon Tetrachloride / adverse effects*
Liver Cirrhosis / pathology*
Male
Models, Biological
Quinolizines / pharmacology*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Smad Proteins / metabolism*
Smad3 Protein / metabolism
Smad7 Protein / metabolism
Transforming Growth Factor beta / metabolism*
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Antiviral Agents; 0/Quinolizines; 0/RNA, Messenger; 0/Smad Proteins; 0/Smad3 Protein; 0/Smad7 Protein; 0/Transforming Growth Factor beta; 16837-52-8/oxymatrine; 56-23-5/Carbon Tetrachloride; EC 2.3.1.48/CREB-Binding Protein
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