| Purpose:To investigate the effect of galangin on cerebral ischemia-reperfusion injury in gerbils,and its mechanism of action on hippocampal neurons.Material and method:60 male gerbils were randomly divided into 5 groups,namely sham operation group,model group,galangin low-dose group(25 mg/kg),galangin mediumdose group(50 mg/kg)and galangin high-dose group(100 mg/kg),the cerebral ischemiareperfusion model was established by ligating bilateral common carotid arteries.Morris water maze(MWM)method was used to evaluate the learning and memory ability of gerbils.Lipid peroxide biomarkers GSH,GSH-Px,MDA,and SOD were used to evaluate the level of lipid peroxidation.Western Blot was used to detect the protein expression levels of SLC7A11 and GPX4.The model in vitro was established by hypoxia and reoxygenation-induced hippocampal neuronal injury,and the MTT method was used to detect neuronal cell viability.The kit detects iron ion content in hippocampal neurons.Immunofluorescence staining and Nissl staining to detect cell morphology.Western Blot to detect protein expression levels of H2 AX,4-HNE,SLC7A11,GPX4,and APP.q RT-PCR to detect changes in m RNA levels of related indicators.Results:In MWM,galangin can improve the learning and memory functions of I/R gerbils.Compared with the model group,galangin(100 mg/kg)group can reduce lipid peroxides in the brains of I/R gerbils level,increased the expression of SLC7A11 and GPX4,decreased cell death,and the difference was statistically significant(P < 0.01).In addition,the expression of Ptgs2,a marker of ferroptosis,in hippocampal neurons of gerbils treated with galangin(100mg/kg),the difference was statistically significant(P < 0.01).After SLC7A11 was silenced,the therapeutic effect of galangin(100 mg/kg)was significantly weakened.Conclusion:1.I/R injury leads to iron overload in hippocampal neurons,increased oxidative stress,and ferroptosis in hippocampal neurons.2.Galangin(100 mg/kg)has a protective effect on brain I/R injury gerbil hippocampal neurons,and its mechanism is to activate the SLC7A11/GPX4 pathway,reduce the level of oxidative stress,and promote lipid peroxide metabolism,thereby inhibiting Hippocampal neuronal ferroptosis. |