Kaempferol alleviates ox-LDL-mediated endothelial cell injury via regulating AMPK/Nrf2/HO-1 signaling pathway / 中国免疫学杂志

ABSTRACT

Objective:To investigate the effects of kaempferol on the oxidized low density lipoprotein(ox-LDL)-induced injury in human umbilical vein endothelial cell (HUVECs) and to explore its underlying molecular mechanism.Methods: HUVECs were randomly divided into 6 groupscontrol group,ox-LDL group,Kaempferol+ox-LDL group,Kaempferol+ox-LDL+Compound C group, Kaempferol+ox-LDL+si-Nrf2 group and Kaempferol+ox-LDL+si-HO-1 group.The cell activity was measured by MTT assay.The cell apoptosis was analyzed by flow cytometry.The protein expression were measured by Western blot.The ROS levels were evaluated by flow cytometry.Results: Compared with control group,ox-LDL treatment decreased the cell viability,increased the cell apoptosis,up-regulated the protein levels of cleaved-caspase 3 and down-regulated the Bcl-2 level,elevated the expression of TNF-α,IL-1β,IL-6, vascular cell adhesion molecule (VCAM1),intercellular adhesion molecule (ICAM1) and selectin E (E-selectin),promoted the reactive oxygen species (ROS) generation and reduced the superoxide dismutase(SOD) levels,and decreased the protein levels of p-AMPK,Nrf2 and HO-1.Compared with the ox-LDL group,kaempferol treatment reversed the ox-LDL-induced cell activity inhibition, apoptosis and oxidative stress damage,and increased the protein levels of p-AMPK,Nrf2 and HO-1.Compound C,si-Nrf2 and si-HO-1 inhibited AMPK/Nrf2/HO-1 signaling pathway,elevated the production of ROS and thus inhibiting the protective effects of kaempferol on ox-LDL-treated HUVECs.Conclusion:Kaempferol alleviates ox-LDL-induced endothelial cell injury,which may be related with the activation of AMPK/Nrf2/ HO-1 signaling pathway.