Abstract: To investigate the protective effects of Procyanidin B2 against hyperlipidemia mediated endothelial cell injury the cellular senescence model was established through saturated fatty acid in vitro.Pancreatic islet endothelial cells (MS-1) were treated with palmitic acid (PA) at 50 μmol/L to establish the senescence model,which were evaluated based on cell viability,senescence-associated β-galactosidase (SA-β-Gal) staining and expression of cell cycle-related genes.To investigate the senescence mechanism of the endothelial cells the proteins related Akt/FoxO4 signaling pathway were detected by immunofluorescence assay.And intervention of cellular senescence by PCB2 was simultaneously studied.The positive cells of SA-β-Gal staining were significantly increased in the MS-1 cells treated with PA.The cell cycle-related genes p21 and p53 were up-regulated which indicated the cell cycle arrest in G0/G1 phase.After intervention with PCB2 (50 μg/mL),cellular senescence could be effectively improved by decreasing p21 and p53 expression.Compared with the control,PA treatment promoted Akt translocation from nucleus to cytoplasm,and FoxO4 translocation into the nucleus.While PCB2 (50 μg/mL) could effectively reverse the translocation of Akt and FoxO4 with PA treatment.PCB2 has a significant protective effect on palmitic acid-induced endothelial cellular senescence,and its possible mechanism may be regulated by the Akt/FoxO4 signaling pathway.

Key words: cellular senescence, procyanidin B2, endothelial cells, Akt, FoxO4