抗癫痫药对成年癫痫患者体内细胞铁死亡的影响

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[中图分类号] R742.1 [文献标志码] A
Effect of antiepileptic drugs on ferroptosis of cells in adult patients with epilepsyWANG Feiyu, ZHONG Rujie,YANG Hailin,LI Xiaoyu,LIU Xue,GAO Jing(Departmentof Neurology,The Afited Hospitalof Qing dao University,Qingdao 266035,China)
[ABSTRACT]ObjectiveToinvestigatetheefectofmonotherapy withvalproicacid(VPA),lamotrigine(LTG)orlevetiracetam(LEV)onferroptosisofcelsinadult patients withepilepsy.MethodsAtotal of95 patients withepilepsy who were treated inDepartmentofNeurologyTheAfiliated HospitalofQingdaoUniversity,fromDecember222 toSeptember024were enroledas epilepsygroup,andaccording tothetypeof thedrug used,they were divided into VPAgroup,LTG group,and LEV group;93individuals,matchedforageandsex,whounderwent physicalexaminationin thesamehospitalduringthesame period of time were enroled as control group.Fasting peripheral venous blood samples were colectedfrom all subjects atbaselineand fromthepatients withepilepsyafter6monthsofmedication.Colorimetrywasused tomeasuretheserumlevelsofferousion (204 (Fe2+) ,glutathione (GSH),and malondialdehyde(MDA),and RT-qPCR and Western blot(WB)were used to measure the expresion levelsof glutathioneperoxidase4(GPX4)and solutecarierfamily7 member11(SLC7A11)in peripheralblood.The aboveindicators werecomparedbetween groups.ResultsAtbaseline,compared withthecontrol group,theepilepsygrouphad significantly higher serum levels of Fe2+ and MDA and significantly lower levels of GSH,GPX4,and SLC7A11 ( t=15.62-18.17 , Z=-6.97-3.16,P<0.05) . After treatment,VPA,LTG,and LEV all significantly reduced the serum levels of Fe2+ and MDA in the epilepsy group (t=5.14-14.75,P<0.05) ,and LTG and VPA induced significantly greater reductions than LEV ( F=5.94 , (204号 7.05,t=-3.56--2.38,P<0.05) . VPA,LTG,and LEV all inhibited the downregulation of GSH,GPX4,and SLC7A1l in peripheral blood (t=3.06-11.15,P<0.05) ,with no significant difference in the degree of such inhibition between the three drugs ( P>0.05) .ConclusionThe threeantiepileptic drugs VPA,LTG,and LEVcan inhibit feroptosis of cels in adult patients with epilepsy,whileLTGandVPAhaveabeterefectthanLEVinimproving ironoverloadandlipidperoxidationduringferroptosis.
[KEY WORDs]Epilepsy;Ferroptosis;Anticonvulsants; Valproic acid; Lamotrigine; Levetiracetam;Treatment outcome;Adult
癫痫是一种具有致残性的慢性神经系统疾病,目前全球癫痫患者已超过7000万人[1]。(剩余11050字)