Abstract: AIM: To investigate the effect and mechanism of ursolic acid on high glucose and high-fat injury of human aortic endothelial cells. METHODS: MTT method was used to select the appropriate injury concentration of high glucose and sodium palmitate and UA pre incubation concentration. The levels of NO and ROS, the release rate of lactate dehydrogenase and the activities of antioxidant enzymes including total superoxide dismutase, catalase and glutathione peroxidase were detected by kit. The expression of endothelial nitric oxide synthase, intercellular adhesion molecule, vascular cell adhesion molecule caspase-1 and GSDMD were detected by Western blot. The protective effect of UA on HAEC was observed. Hoechst33342 combined with PI fluorescence staining was used to detect the whole state of cell membrane to explore the occurrence of pyroptosis. RESULTS: Pre-incubation with UA (1 and 5 μmol/L) could reduce the damage of HAEC caused by high glucose and high fat (30 mmol/L Glu + 0.1 mmol/L SPA), enhance HAEC activity, increase NO release and eNOS protein expression, alleviate oxidative stress injury, reduce the protein expression of adhesion molecules and reduce the occurrence of pyroptosis. CONCLUSION: UA may reduce the damage of endothelial cells by inhibiting the oxidative stress response and the occurrence of pyroptosis induced by high glucose and high fat.

Key words: ursolic acid, human aortic endothelial cells, high glucose and high lipid, oxidative stress, pyroptosis