Abstract: Objective To study the protective effect of Nox1/4 inhibitor on dysfunction of EA.hy926 human umbilical vein fusion cells induced by lipopolysaccharide. Methods EA. hy926 cells were divided into control group, LPS group, Nox1/4 inhibitor (GKT137831) +LPS group. CCK8 assay was used to detect cell viability, LDH and NO content in culture medium, ROS level in cells was detected by immunofluorescence, IL-1β and IL-6 secretion by ELISA, and endoplasmic reticulum stress marker protein expression was detected by Western blot. Results Compared with the control group, the release of NO, ROS and inflammatory factors IL-1β and IL-6 in LPS group increased significantly (P < 0.05), while the release of NO, IL-1β and IL-6 decreased significantly after Nox1/4 inhibitor intervention (P < 0.05). Compared with the control group, the expression of GRP78, p-PERK, ATF6 and IREα was up-regulated and endoplasmic reticulum stress was significantly activated in LPS group. The intervention of Nox1/4 inhibitor could inhibit the decrease of endoplasmic reticulum stress marker protein expression induced by LPS. Conclusion Inhibition of Nox1/4 attenuates LPS-induced endoplasmic reticulum stress injury in EA.hy926 cells. The mechanism may be that Nox1/4 inhibitor may reduce the production of ROS from Nox1/4, inhibit endoplasmic reticulum stress, alleviate inflammatory response and improve endothelial function.

Key words: Nox1/4, Endothelial cell injury, lipopolysaccharide, oxidative stress, endoplasmic reticulum stress