2012•Chinese journal of integrated traditional and Western medicineRequires access
Effect of gypenosides on MMPs and TIMPs in liver fibrosis induced by carbon tetrachloride in rats
Jinghua Peng
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Abstract
Objective:To investigate the effect of gypenosides on matrix metalloproteinases(MMPs)and tissue inhibitors of metalloproteinases(TIMPs) in liver fibrosis induced by carbon tetrachloride(CCl4) in rats.Methods:Liver fibrosis in rats was induced by CCl4 subcutaneous injection for 9 weeks,3mg/kg of 100% CCl4 for the first time and 2ml/kg of 50% CCl4-olive oil solution,twice per week.At the beginning of the 7th week,rats stimulated by CCl4 were divided into model group(n=12),gypenosides group(n=11) and colchicine group(n=11).Meanwhile,rats in gypenosides and colchicine group were administrated with gypenosides(200mg·kg-1·d-1) and colchicine(0.1mg·kg-1·d-1) respectively and the others were administrated with sterile water.At the end of the 9th week,hepatic hydroxyproline(Hyp)was test and the collagen deposition in liver tissue were observed as well as hepatic α-smooth muscle actin(α-SMA),MMP-2,MMP-9,TIMP-1 and TIMP-2.Results:At the end of the experiment,there were two rats died in the model group and no death in gypenosides and colchicine group.With stimulation by CCl4,hepatic Hyp content increased significantly and decreased in gypenosides and colchicine group.Obvious collagen deposition in liver tissue was observed in model group and alleviated by gypenosides and colchicine treatment.The positive staining of hepatic α-SMA,activity of MMP-2 and MMP-9 as well as protein expression of TIMP-1 and TIMP-2 were all up-regulated in model group.After administration with gypenosides,positive staining of α-SMA in liver tissue was inhibited as well as the activity of MMP-2 and MMP-9 and protein expression of TIMP-1 and TIMP-2.The inhibitory effects of colchicine on α-SMA,MMP-2 and MMP-9 were also observed.Conclusion:Gypenosides can alleviate liver fibrosis induced by CCl4 in rats which probably related to its inhibitory effects on hepatic stellate cell activation and the activity of MMP-2,MMP-9 as well as the protein expression of TIMP-1 and TIMP-2.