Exendin-4 ameliorates high glucose- and TNF-α-induced vascular endothelial cell damage by inhibiting p38 MAPK and NF-κB p65 translocation / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effects of exendin-4 on vascular endothelial cells and explore the possible mechanism.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 (P<0.01). 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 (P<0.01).</p><p><b>CONCLUSION</b>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.</p>