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基于ERK-mTOR通路调控自噬探讨六味地黄丸减轻成骨细胞氧化应激损伤的分子机制摘要：自噬是一种维持细胞稳态的重要机制，而ERK/mTOR通路则是自噬的主要调节途径之一。六味地黄丸是一种常用的中药方剂，已被广泛应用于临床治疗骨质疏松等疾病。本文旨在研究ERK/mTOR通路在六味地黄丸调控自噬中的作用，并探究六味地黄丸对成骨细胞氧化应激损伤的分子机制。本研究使用成骨细胞进行体外实验，并使用Westernblot、免疫荧光等技术对细胞的生理指标进行分析。结果显示，六味地黄丸可以通过抑制ERK/mTOR通路来促进自噬的发生，并通过降低ROS水平来减轻成骨细胞氧化应激损伤。该研究结果增加了对六味地黄丸调控自噬的认识，为其在临床应用中提供了分子基础。
关键词：ERK/mTOR通路；自噬；六味地黄丸；成骨细胞；氧化应激；ROS水平
Abstract:Autophagyisanimportantmechanismformaintainingcellularhomeostasis,andtheERK/mTORpathwayisoneofthemainregulatorypathwaysofautophagy.LiuweiDihuangWanisacommonlyusedtraditionalChinesemedicineformulaandhasbeenwidelyusedintheclinicaltreatmentofosteoporosisandotherdiseases.TheaimofthisstudywastoinvestigatetheroleoftheERK/mTORpathwayintheregulationofautophagybyLiuweiDihuangWanandtoexplorethemolecularmechanismofLiuweiDihuangWaninreducingoxidativestressdamageofosteoblasts.Invitroexperimentswereperformedusingosteoblasts,andthephysiologicalindicatorsofcellswereanalyzedusingWesternblot,immunofluorescence,andothertechniques.TheresultsshowedthatLiuweiDihuangWancanpromotetheoccurrenceofautophagybyinhibitingtheERK/mTORpathwayandreduceoxidativestressdamageofosteoblastsbyreducingtheROSlevel.ThisstudyincreasesourunderstandingoftheregulationofautophagybyLiuweiDihuangWanandprovidesamolecularbasisforitsclinicalapplication.
Keywords:ERK/mTORpathway;autophagy;LiuweiDihuangWan;osteoblast;oxidativestress;ROSleveLiuweiDihuangWanisawell-knowntraditionalChinesemedicinethathasbeenusedformanyyearsinthetreatmentofvariousdiseases,especiallythoserelatedtothekidneyandbone.However,itsmechanismofactionremainsunclear.Inthisstudy,weinvestigatedtheeffectofLiuweiDihuangWanonautophagyandoxidativestressinosteoblasts.
Autophagyisahighlyconservedcellularprocessthatplaysanimportantroleinmaintainingintracellularhomeostasisbyeliminatingdamagedorganellesandlargemolecularproteincomplexes.Ithasbeensuggestedthatautophagydysregulationmaycontributetothepathogenesisofvariousdiseases,includingbone-relateddiseases.Inthisstudy,wefoundthatLiuweiDihuangWancanpromoteautophagyinosteoblastsbyinhibitingtheERK/mTORpathway,whichisawell-knownnegativeregulatorofautophagy.OurresultsprovideanovelmechanismfortheregulationofautophagybyLiuweiDihuangWan.
Oxidativestress,whichisdefinedasanimbalancebetweentheproductionofreactiveoxygenspecies(ROS)andthecellularantioxidantdefensesystem,isknowntoplayacrucialroleinthedevelopmentofvariousdiseases,includingosteoporosis.Inthisstudy,wefoundthatLiuweiDihuangWancanreduceoxidativestressdamageinosteoblastsbyreducingtheROSlevel.OurresultsprovideanewinsightintothepotentialtherapeuticapplicationofLiuweiDihuangWaninthetreatmentofosteoporosis.
Inconclusion,ourstudyprovidesevidencethatLiuweiDihuangWancanpromoteautophagyandreduceoxidativestressdamageinosteoblastsbyregulatingtheERK/mTORpathwayandROSlevel,respectively.ThesefindingshighlightthepotentialofLiuweiDihuangWanasatherapeuticagentforthetreatmentofbone-relateddiseases,especiallyosteoporosis.FurtherstudiesareneededtoconfirmtheclinicalefficacyandsafetyofLiuweiDihuangWanasatreatmentforosteoporosisOsteoporosisisacommonskeletaldisorderthatischaracterizedbylowbonedensity,increasedbonefragility,andanincreasedriskoffractures.Itisamajorhealthproblemamongelderlypeopleworldwide,anditsprevalenceisexpectedtoriseinthecomingyearsduetoanagingpopulation.Osteoporosiscanseriouslyaffectthequalityoflifeofaffectedindividuals,anditisassociatedwithsignificanthealthcarecosts.
Thecurrenttreatmentsforosteoporosisincludelifestylemodifications,calciumandvitaminDsupplementation,anddrugtherapy.However,thesetherapieshavelimitations,andtheirefficacyandsafetyarenotalwayssatisfactory.Therefore,thereisaneedforthedevelopmentofnewandeffectivetreatmentsforosteoporosis.
TraditionalChinesemedicine(TCM)hasbeenusedforcenturiestotreatvariousdiseases,includingosteoporosis.LiuweiDihuangWanisaTCMformulathathasbeenusedtotonifythekidneyandnourishtheliverforthetreatmentofvariousailments,includingosteoporosis.Itiscomposedofsixherbalingredients,namely,Rehmanniaglutinosa,Cornusofficinalis,Dioscoreaopposita,Alismaorientale,Poriacocos,andPaeoniasuffruticosa.
Inrecentyears,studieshavesuggestedthatLiuweiDihuangWanmayhaveabeneficialeffectonbonehealth.Themechanismsunderlyingitseffectsonbonemetabolismarenotfullyunderstood,butrecentresearchhassuggestedthatLiuweiDihuangWanmaypromoteautophagyandreduceoxidativestressdamageinosteoblastsbyregulatingtheERK/mTORpathwayandROSlevel,respectively.
Autophagyisafundamentalcellularprocessthatplaysacriticalroleinmaintainingcellularhomeostasisbydegradingdamagedorganellesandproteins.Ithasbeensuggestedthatimpairedautophagyisinvolvedinthepathogenesisofosteoporosis.LiuweiDihuangWanhasbeenshowntopromoteautophagyinosteoblasts,whichmaycontributetoitsbeneficialeffectsonbonehealth.
Oxidativestressisaconditioninwhichthereisanimbalancebetweentheproductionofreactiveoxygenspecies(ROS)andtheabilityofcellstoneutralizethem.ROScancausedamagetocellsandtissues,andhavebeenimplicatedinthedevelopmentofvariousdiseases,includingosteoporosis.LiuweiDihuangWanhasbeenshowntoreduceoxidativestressdamageinosteoblasts,whichmaycontributetoitsbeneficialeffectsonbonehealth.
TheERK/mTORpathwayisasignalingpathwaythatplaysacriticalroleincellgrowthandsurvival.Dysregulationofthispathwayhasbeenimplicatedinthepathogenesisofvariousdiseases,includingosteoporosis.LiuweiDihuangWanhasbeenshowntoregulatetheERK/mTORpathwayinosteoblasts,whichmaycontributetoitsbeneficialeffectsonbonehealth.
Overall,theavailableevidencesuggeststhatLiuweiDihuangWanmayhaveabeneficialeffectonbonehealthbypromotingautophagyandreducingoxidativestressdamageinosteoblastsbyregulatingtheERK/mTORpathwayandROSlevel,respectively.FurtherstudiesareneededtoconfirmtheclinicalefficacyandsafetyofLiuweiDihuangWanasatreatmentforosteoporosis.Ifproveneffective,LiuweiDihuangWanmayprovideanalternativeorcomplementarytherapyforosteoporosispatientsAdditionally,LiuweiDihuangWanhasshownpotentialinimprovingcognitivefunctionandreducingoxidativestressinthebrain.Studieshavefoundthatitsactivecompounds,suchascatalpolandloganin,exhibitneuroprotectiveeffectsbymodulatingseveralsignalingpathwaysinvolvedinneuronalfunctionandsurvival.LiuweiDihuangWanhasalsobeenreportedtoenhancememoryandlearningabilityinanimalmodelsofAlzheimer'sdiseaseandage-relatedcognitivedecline.
Moreover,LiuweiDihuangWanhasbeenusedinTraditionalChineseMedicineforitsanti-inflammatoryandimmune-modulatingproperties.Ithasbeenfoundtoinhibittheproductionofinflammatorycytokinesandpromotetheactivityofimmunecells,suggestingitspotentialintreatingimmune-relateddisorderssuchasrheumatoidarthritisandlupus.
However,despitethesepotentialhealthbenefits,thereisaneedforfurtherstudiestoinvestigatethesafetyandefficacyofLiuweiDihuangWaninhumans.Adverseeffectsanddruginteractionsmayalsooccurwithprolongeduseorhighdosesoftheherbalmedicine.
Inconclusion,LiuweiDihuangWanisatraditionalChi
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