芒柄花素通过影响ACSL4/LPCAT3/GPX4表达缓解脑缺血再灌注损伤中神经元铁死亡

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[关键词]脑缺血再灌注损伤；芒柄花素；铁死亡；ACSL4/LPCAT3/GPX4轴；神经保护 [中图分类号]R285.5 [文献标志码]A [文章编号]doi：10.3969/j.issn.1674-070X.2025.06.001

Formononetin alleviates neuronal ferroptosis in cerebral ischemiareperfusion injury by modulating ACSL4/LPCAT3/GPX4 expression

MA Qiang'， OUYANG Xinyi'， YAN Siyang²， LIU Lijuan²， ZHOU Desheng²* 1.HunanUniversityofChineseMedicine，ChangshaHunan41O2O8，China;2.TheFirstHospitalofHunanUniersityof Chinese Medicine，Changsha， Hunan 41ooo7，China

[Abstract]Objective Toinvestigatewhetherformononetinexertsneuroprotectivefectsincerebral ischemia-reperfusion injury（CIRI）byregulatingtheACSL4/LPCAT3/GPX4signalingaxistoinhibitneuronalferoptosis.MethodsThemodifiedsuture methodwasused to establish aratmodel of midlecerebral arteryocclusion/reperfusion （MCAO/R）.Ashamoperationgroup，a model group，low-，medium-，andhigh-doseformononetin （FMN）groups，andanedaravonecontrolgroupweresetup.Neurological functionwasasessedusingtemodifiedurologcalseveritycoe（m）Hstopathologicalchangesinbraintisseeeaated byHE，Nissl，and silver staining.Neuronal apoptosis was detected by TUNEL staining.The levels of Fe2+ MDA，LPO，GSH/GSSG， andROSweresiultaneouslymeasuredtoessferoptosishileWsternblotfocyometryndiunofluorescnceere usedtodetecttheexpressonofkeyferoptosis-relatedproteinsResultsComparedwithtemodelgroup，formononetinsignifiantly improvedheurologicaldeficitsandhistopathologicalchangesinatseducedtheproportionofapoptoticcellsandrotosis related indicators （ Fe2+ ，MDA， LPO， ROS）， and increased antioxidant level （GSH/GSSG） P- <0.05， P<0.01 1）.flow cytometry results showed that formononetin significantly reduced the expression ratio of ACSL4/LPCAT3 double-positive cells （P<0.01 ；immunofluorescence resultsshowed that formononetin reduced the expression levels of ACSL4 and LPCAT3 in brain tissue（ P- <0.05， P≪0.01 1）.Conclusion Formononetincaninhibit feroptosis byregulating theexpressionofACSL4/LPCAT3/GPX4，allviatenerveinjuycausedbyCIRI and provide theoretical support for its application in the adjuvant treatment of ischemic stroke.

[Keywords]cerebral ischemia-reperfusion injury;formononetin; feroptosis;ACSL4/LPCAT3/GPX4axis;neuroprotection

脑缺血再灌注损伤（cerebral ischemia-reperfu-sioninjury，CIRI是急性脑卒中，特别是缺血性脑卒中的重要发病机制之一，其发生机制复杂，涉及多种细胞死亡方式、炎症反应、氧化应激与自由基损伤等环节[1-2]。（剩余17149字）