Exendin-4 ameliorates high glucose- and TNF-α-induced vascular endothelial cell damage by inhibiting p38 MAPK and NF-κB p65 translocation

Objective To investigate the protective effects of exendin-4 on vascular endothelial cells and explore the possible mechanism.Methods Human umbilical vascular endothelial cells(HUVECs) were cultured in the presence of high glucose and tumor necrosis factor-α(TNF-α,10 ng/ml) with or without exendin-4.The level of nitric oxide(NO) in the cell culture supernatant was measured using a nitrate reductase method.The expression of intercellular adhesion molecule-1(ICAM-1) mRNA was measured by real-time PCR,and nuclear factor-κB(NF-κB) p65 translocation was detected using immunofluorescence assay.Western blotting was employed to measure the expression of p38 MAPK protein in the treated cells.Results In the presence of high glucose and TNF-α,treatment of cells with exendin-4 did not obviously affect the cellular synthesis of NO,but significantly down-regulated the expression of ICAM-1 mRNA(P0.01).The nuclear fluorescence intensity of NF-κB p65 and the expression level of p38 MAPK protein in the cells were significantly lowered by exendin-4 treatment(P0.01).Conclusion Exendin-4 ameliorates high glucose-and TNF-α-induced HUVEC-12 cell damage by inhibiting the expression of p38 MAPK protein and translocation of NF-κB p65.