芒柄花素通過影響ACSL4/LPCAT3/GPX4表達(dá)緩解腦缺血再灌注損傷中神經(jīng)元鐵死亡
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[關(guān)鍵詞]腦缺血再灌注損傷；芒柄花素；鐵死亡；ACSL4/LPCAT3/GPX4軸；神經(jīng)保護(hù) [中圖分類號]R285.5 [文獻(xiàn)標(biāo)志碼]A [文章編號]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
腦缺血再灌注損傷（cerebral ischemia-reperfu-sioninjury，CIRI是急性腦卒中，特別是缺血性腦卒中的重要發(fā)病機(jī)制之一，其發(fā)生機(jī)制復(fù)雜，涉及多種細(xì)胞死亡方式、炎癥反應(yīng)、氧化應(yīng)激與自由基損傷等環(huán)節(jié)[1-2]。（剩余17149字）