Abstract: 【Objective】 To discuss the role of NOX4 signaling pathway in the antagonistic mechanism of Glucagon-like Peptide-1 against the oxidative damage on vascular endothelial cells induced by advanced glycation endproducts. 【Method】 Experimental group was divided into a control group

AGE group

AGE + GLP-1 group

AGE +NOX4 siRNA group and AGE + negative control siRNA group. The expression of NOX4 mRNA was detected by RT-PCR. The expression of NOX4 protein was detected by Western blotting. The apoptosis rate and the levels of ROS were detected by flow cytometry. 【Results】 Compared with control group

AGE significantly promoted the expression of NOX4 protein(P = 0.001) and NOX4 mRNA(P < 0.05). After added GLP-1 into the AGE group

it significantly inhibited the expression of NOX4 protein (P = 0.003) and NOX4 mRNA (P < 0.05). Compared with AGE group

NOX4 siRNA inhibited the ROS generation (P = 0.011)

the apoptosis of endothelial cells (P < 0.05). Negative control RNA had no influence on the ROS generation (P = 0.958)

the apoptosis of endothelial cells (P = 0.169). 【Conclusion】 GLP-1 antagonize oxidative damage on human umbilical endothelial cells induced by advanced glycation endproducts at least partly through inhibiting the expression of NOX4 protein.