Abstract:

 Objective   To observe the therapeutic effect of grape seed proanthocyanidin  extract (GSPE) on Carbon tetrachlorideinduced hepatic fibrosis in rats and explore its therapeutic mechanism．Methods   20 of 50 rats were randomly selected as the control group (n=10) and the solvent group (n=10). The remaining 30 rats were regarded as models of hepatic fibrosis which were established by intraperitoneal injection of carbon tetrachloride twice a week for 8 weeks. The 24 successful model rats were divided into the model group (n=12) and the GSPE group (n=12), with GSPE 150mg/(kg·d) being given to the GSPE group rats from 5th week. After eight weeks, all rats were executed, and the liver and serum were stored for further investigation.Serum alanine  aminotransferase (ALT)、aspartate aminotransferase (AST) and total bilirubin (TBIL)  were tested by automatic biochemical analyzer. Hexadecenoic acid (HA) 、 laminin (LN)  and Procollagen Ⅲ (PCⅢ) were tested by radioimmunoassay. Hydroxyproline (HyP) was tested by liver tissue alkaline hydrolysis. Superoxide dismutase (SOD) 、malondialdehyde (MDA) and reduced glutathione hormone (GSH) were determined by chemical colorimetric method．Additionally, liver samples from fixed part were stained by HE to trace the degree of fibrosis．Results   Levels of serum ALT、AST、TBIL、HA、LN、PCⅢ in the rats of the model group were significantly raised(P<0.05) compared to those of the control group. Activities of  GSH and SOD in hepatic tissue decreased and levels of MDA and Hyp obviously increased (P<0.05)．Levels of serum ALT、AST 、TBIL、HA、LN、PCⅢ in the GSPE group were significantly reduced (P<0.05) in comparison to those of the model group. Activities of GSH and SOD in hepatic tissue increased and levels of MDA and Hyp decreased (P<0.05). In addition, the GSPE group had significantly improved histological changes of hepatic fibrosis(P<0.05). Conclusion   GSPE plays an inhibitory role in CCL4-induced  hepatic fibrosis in  rats,  probably through protection of hepatic cell, alleviation of injury induced by lipid peroxidation and inhibition on collagen fiber synthesis.

Key words: Grape seed proanthocyanidin extract； Hepatic fibrosis； Hepatic stellate cell； Carbon tetrachloride； Model rats