Trimetazidine Decreases Lipopolysaccharide-induced Damage In Human Umbilical Vein Endothelial Cells Through Activation Of Nrf2 And Suppression Of Inflammasome

Objectives: Trimetazidine(TMZ)can reduce oxygen consumption and enhance the tolerance of tissues to hypoxia,which is widely used in the treatment of angina pectoris.TMZ can protect vascular endothelial cells through antioxidant free radicals.Research suggests that cardiovascular disease is closely related to vascular endothelial cell damage.We use Lipopolysaccharide(LPS)to induce human umbilical vein endothelial cells(HUVECs)injury,further to explore whether TMZ pretreatment could improve LPS induced HUVECs injury and the underlying mechanisms.Methods: HUVECs were divided into the following groups: control group?LPS group(LPS stimulation group)?LPS plus TMZ 50umol/L group?LPS plus TMZ 100umol/L group?LPS plus TMZ 250umol/L group.We carried out e Du assay to detect cell proliferation function.Transwell test was performed to detect cell migration function.The expression levels of Nrf2 and NLRP3,IL-1? in different groups of cells were detected by Westernblot.Results: e Du experiment and transwell experiment showed that LPS reduced cell proliferation function,cell migration,and TMZ pretreatment could improve proliferation function and cell migration.Westernblot indicated that LPS stimulation reduced the expression levels of Nrf2 and upregulated the expression levels of NLRP3 and IL-1?.TMZ pretreatment upregulated the expression of Nrf2 and reduced the expression of NLRP3 and IL-1?.Conclusion: TMZ improve LPS induced HUVECs damage via activating Nrf2 and regulating the expression of NLRP3?IL-1?.Our results suggest that TMZ can attenuate LPS induced inflammation,improve cell function.