ABSTRACT
Objective To study the effect of geniposide(Gen)on the proliferation,migration and angiogenesis of human retinal vascular endothelial cells(hRVECs)induced by high glucose and explore its mechanism.Methods The hRVECs were intervened with different concentrations(0,1,5,10,20,40 and 80 mg·L-1)of Gen for 24 h,and Cell Counting Kit-8(CCK-8)was used to detect the effect of Gen on the proliferation activity of hRVECs.The hRVECs were di-vided into the control group,high glucose(25 mmol·L-1)group,low,middle and high Gen concentration(5,10 and 20 mg·L-1)groups,bevacizumab(BEV,250 μg·L-1)group and high Gen concentration+BEV(250 pg·L-1)group.Cell proliferation activity was detected by CCK-8.The cell migration ability was detected by scratch test.The tube formation ability of cells was detected by the in vitro tube formation assay.The protein expression levels of vascular endothelial growth factor-A(VEGF-A),soluble VEGF receptor-1(sFlt-1),matrix metalloproteinase 2(MMP-2)and matrix metallo-proteinase 9(MMP-9)in cells were detected by Western blot.Results Compared with 0 mg·L-1 Gen,there was no sta-tistically significant difference in the effect of Gen with concentrations of 1,5,10,20,40 and 80 mg·L-1 on the prolifera-tion activity of hRVECs(all P＞0.05).Compared with the control group,the proliferation activity and migration ability of hRVECs in the high glucose group were significantly enhanced(both P＜0.05),the cell circular structure increased,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly increased(all P＜0.05),and the protein expression level of sFlt-1 significantly decreased(P＜0.05).Compared with the high glucose group,the proliferative activity and mi-gration ability of cells in all Gen concentration groups and BEV group significantly decreased(all P＜0.05),the circular structure of cells was reduced,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly decreased(all P＜0.05),and the protein expression level of sFlt-1 significantly increased(P＜0.05).Compared with the high Gen concentra-tion group,the high Gen concentration+BEV group showed a significant decrease in cell proliferation activity(P＜0.05),a decrease in cell circular structure,a significant decrease in VEGF-A,MMP-2 and MMP-9 protein expression levels(all P＜0.05),and a significant increase in sFlt-1 protein expression level(P＜0.05).Conclusion Gen can inhibit the high glucose-induced proliferation,migration and angiogenesis of hRVECs,and its mechanism may be related to the regulation of VEGF/sFlt-1 axis balance.