芍药内酯苷介导Nrf2/GPX4信号轴调控肝细胞铁死亡的作用机制OA

Objective To investigate the mechanism by which albiflorin(ALB)regulates hepatocyte ferroptosis via mediating Nrf2/GPX4 signaling axis.Methods A ferroptosis model was established by inducing AML-12 hepatocyte injury with H2 O2,and ALB was used as the intervention agent.After AML-12 cells were stimulated with H2 O2 for 2 h,ALB was added at final concentrations of 25 and 50 μmol/L,respectively,followed by continuous culture for 24 h.Cell viability was determined via MTT assay.The expression levels of Nrf2,GPX4 and SLC7A11 were analyzed by Western blot and RT-qPCR.The levels of GSH,ROS and labile iron were measured by ELISA to evaluate the regulatory effect of ALB on ferroptosis.Results ALB could up-regulate the expression levels of Nrf2,GPX4 and SLC7A11 in AML-12 hepatocytes.ALB could significantly regulate intracellular GSH-PX activity,ROS level,ferrous ion(Fe2+)content and iron metabolism-related pathways.Through the above multiple regulatory mecha-nisms,ALB could effectively inhibit H2 O2-induced hepatocyte ferroptosis.Conclusion ALB can inhibit H2 O2-induced ferroptosis in AML-12 hepatocytes by regulating Nrf2/GPX4 signaling axis.Based on its intervention in hepatocyte ferroptosis and potential protective effect against hepatic injury,ALB is expected to serve as a promis-ing candidate drug for anti-hepatic injury therapy.