Dauracine Inhibits Ferroptosis In Nerve Cells Effect On Brain Injury After Intracerebral Hemorrhage

Objective: To prove that dauracine can reduce brain injury after intracerebral hemorrhage by inhibiting ferroptosis of nerve cells.Methods:Ferroptosis was induced by 5μM RSL3 in SH-SY5 Y cells,and then the survival rate,reactive oxygen species(ROS),iron level,lipid reactive oxygen species level,GPX4 expression were detected after it was administered by 0.03 μM,0.3μM and 3μM of dauracine,respectively.Then,SH-SY5 Y cell line of Si GPX4 was constructed by transfection of plasmid,and ferroptosis was induced by 5μM RSL3,and the expression of GPX4 in each group was detected after it was administered by 0.03 μM,0.3μM,and 3μM dauracine intervention.The mouse model of intracerebral hemorrhage(ICH)was established by stereotaxic injection of collagenase,and then the mouse model was injected with 5mg/kg,10mg/kg and 15mg/kg dauracine in the tail vein.The experimental groups were divided into: sham operation group,ICH group,5mg/kg,10mg/kg and 15mg/kg dauracine treatment group.The behavior test,brain water content,iron level,MDA level and blood-brain barrier permeability of ICH mice in each group were evaluated,and the brain tissues of ICH mice were observed and analyzed by MRI,pathology and Western blot.Results: Dauracine could inhibit ferroptosis induced by RSL3 in SH-SY5 Y cells to a certain extent,inhibit the increase of ferroptosis-related factors and up-regulate the expression of GPX4 to a certain extent.In vivo experiments have also found that dauracine can alleviate neurological function injury,intracerebral edema and intracerebral hematoma caused by intracerebral hemorrhage to a certain extent,repair the blood-brain barrier,reduce neuronal death,and reduce iron and MDA levels related to ferroptosis,and at the same time up-regulate GPX4 expression.Conclusion:Dauracine can inhibit ferroptosis of nerve cells and alleviate brain injury after intracerebral hemorrhage by up-regulating the expression of GPX4.