Effect Of Vascular Endothelial Growth Factor On Intrahepatic Colonization Of Bone Marrow Mesenchymal Stem Cells After Transplantation In Fibrosis Rats

Objective: To explore the intrahepatic colonization of Bone Marrow Mesenchymal Stem Cells(BMSCs)and the therapeutic for liver fibrosis under Vascular Endothelial Growth Factor influence on fibrosis rats.Methods: Rat BMSCs were isolated,cultured,characterized,in vitro.Before transplanted into liver,BMSCs were labeled by CM-Dil.Rat liver fibrosis models were induced by CCl4 injected intraperitoneally and were divided into four groups: group A(saline treated,n=6),group B(VEGF was injected by tail vein,n=6),group C(BMSCs were transplanted through the portal vein),group D(combined with both treatments of group B and group C,n=6).After one month treated,three rats were selected from each group randomly for measuring liver vascular permeability by Evans Blue Dye method.The other rats were sacrificed.Liver tissue samples were taken for examinations.Find out the differences of liver vascular permeability,intrahepatic colonization of VEGF&Vcam-1,liver function and level of liver fibrosis in four groups after treatment.We obtained the fibrosis degree by H&E,Sirius red and Masson staining.The expression of ?-SMA,Collagen ?,VEGF,Vcam-1,Ki67,PCNA was measured by immunofluorescence assay,Col3?1,IL6,Vimentin,Twist1,Snail,Slug,ECadherin,Occludin,VEGF,Vcam-1,ALB and G6 Pase were analyzed by real-time PCR.Western Blot was used to test the protein degree of TGF-?,?-SMA,Collagen ?,VEGF,Vcam-1,CYP3A1 and ALB.Results: The results related to rats liver fibrosis in four groups demonstrated that,the degree of liver fibrosis improved significantly in group D?Measurement of vascular leakage with the Evans Blue dye showed a marked increase in plasma permeability was found in group D and group B as compared with other two groups.The immunofluorescence assay result showed the expression of VEGF and Vcam-1 had increased in group D.WB and q RT-PCR revealed the same consequence(P<0.05).The rats of Group C and Group D were transplantated BMSCs,the fluorescent tracer technique showed that BMSCs mainly appeared in portal area in Group C and fluorescence dispersedly appeared in hepatic lobule in Group D.The value of Ki67,PCNA,CYP3A1,ALB and G6 Pase of rats in Group D had significant improved compared with Group A and Group C(P<0.05).Conclusion:1.VEGF promotes the intrahepatic colonization of BMSCs in fibrosis liver?2.VEGF augments BMSCs ability to repair liver cirrhosis and improve liver regeneration.