首页|Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline on bile duct ligation induced liver fibrosis in rats
Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline on bile duct ligation induced liver fibrosis in rats
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NETL
NSTL
万方数据
维普
AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)-induced liver fibrosis in rats.METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wk via a osmotic minipump (Alzet 2ML4) immediately after BDL operation.After scarifying,serum and liver specimens were collected.Hematoxylin and eosin staining,Sirius red staining,enzyme linked immunosorbent assay,Western blot or real-time polymerase chain reaction were used to determinate liver functions,histological alterations,collagen deposition,mRNA expression of markers for fibroblasts,transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7).RESULTS:When compared to model rats,chronic exogenous AcSDKP infusion suppressed profibrogenic TGF-β1 signaling,α-smooth muscle actin positivity (α-SMA),fibroblast specific protein-1 (FSP-1) staining and collagen gene expression.Col Ⅰ,Col Ⅲ,matrix metalloproteinase-2,tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10 vs 14.16 ± 6.50,2.02 ± 0.45 vs 10.00 ± 3.35,2.91 ± 0.30 vs 7.83 ± 1.10,4.64 ± 1.25 vs 18.52 ± 7.61,0.46 ± 0.16 vs 0.34 ± 0.12,respectively,P ＜ 0.05).Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury,inflammation and fibrosis.BDL caused a remarkable increase in alanine transaminase,aspartate transaminase,total bilirubin,and prothrombin time,all of which were reduced by AcSDKP infusion.Mast cells,collagen accumulation,α-SMA,TGF-β1,FSP-1 and BMP-7 increased.The histological appearance of liver specimens was also improved.CONCLUSION:Infusion of exogenous AcSDKP attenuated BDL-induced fibrosis in the rat liver.Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
NETL
NSTL
万方数据
维普
