清達(dá)顆粒通過(guò)調(diào)控p38MAPK-Nrf2-HO-1通路減輕脂多糖誘導(dǎo)的小膠質(zhì)細(xì)胞氧化應(yīng)激反應(yīng)

清達(dá)顆粒通過(guò)調(diào)控p38MAPK-Nrf2-HO-1通路減輕脂多糖誘導(dǎo)的小膠質(zhì)細(xì)胞氧化應(yīng)激反應(yīng)摘要：脂多糖（LPS）是一種重要的氧化應(yīng)激源，其可以誘導(dǎo)小膠質(zhì)細(xì)胞（microglia）產(chǎn)生大量的氧化物和炎癥因子，從而導(dǎo)致神經(jīng)炎癥和神經(jīng)退行性疾病。本文旨在探討清達(dá)顆粒通過(guò)調(diào)控p38MAPK/Nrf2/HO-1通路對(duì)脂多糖誘導(dǎo)的小膠質(zhì)細(xì)胞氧化應(yīng)激反應(yīng)的影響。實(shí)驗(yàn)采用小鼠BV2微腦膠質(zhì)瘤細(xì)胞系，利用MTT法檢測(cè)清達(dá)顆粒的細(xì)胞毒性；利用ELISA法檢測(cè)不同濃度LPS對(duì)BV2細(xì)胞TNF-α、IL-1β分泌的影響；采用Westernblotting分析清達(dá)顆粒對(duì)LPS誘導(dǎo)BV2細(xì)胞p38MAPK、Nrf2/HO-1信號(hào)通路產(chǎn)生的影響。結(jié)果表明，清達(dá)顆粒對(duì)BV2細(xì)胞無(wú)細(xì)胞毒性，可以抑制LPS誘導(dǎo)的TNF-α、IL-1β分泌；同時(shí)，清達(dá)顆粒增加了LPS誘導(dǎo)的BV2細(xì)胞Nrf2和HO-1表達(dá)。實(shí)驗(yàn)結(jié)果提示清達(dá)顆粒通過(guò)p38MAPK/Nrf2/HO-1信號(hào)通路的調(diào)控來(lái)減輕LPS誘導(dǎo)的小膠質(zhì)細(xì)胞氧化應(yīng)激反應(yīng)，從而具有一定的治療價(jià)值。

關(guān)鍵詞：清達(dá)顆粒，脂多糖，小膠質(zhì)細(xì)胞，氧化應(yīng)激反應(yīng)，p38MAPK，Nrf2，HO-1。

Abstract:Lipopolyssacharides(LPS)isanimportantoxidantstresssourcethatcaninducemicroglialcellstoproducelargeamountsofoxidativesubstancesandinflammatoryfactors,leadingtoneuroinflammationandneurodegenerativediseases.ThispaperaimstoexploretheimpactofQindaparticlesonLPS-inducedoxidativestressresponsesinmicroglialcellsbyregulatingp38MAPK/Nrf2/HO-1pathway.ThesmallmouseBV2microglialtumorcelllinewasusedintheexperiment,andMTTassaywasusedtodetectthecytotoxicityofQindaparticles.ELISAwasusedtodetecttheeffectsofdifferentconcentrationsofLPSonTNF-αandIL-1βsecretioninBV2cells,whileWesternblottingwasusedtoanalyzetheeffectsofQindaparticlesonLPS-inducedp38MAPK,Nrf2/HO-1signalpathwayinBV2cells.TheresultsshowedthatQindaparticleshadnocytotoxicitytoBV2cells,andcouldinhibitthesecretionofTNF-αandIL-1βinducedbyLPS.Meanwhile,QindaparticlesincreasedNrf2andHO-1expressioninBV2cellsinducedbyLPS.TheexperimentalresultssuggestthatQindaparticlescanalleviateLPS-inducedoxidativestressresponsesinmicroglialcellsthroughtheregulationofp38MAPK/Nrf2/HO-1signalpathway,andhavecertaintherapeuticvalue.

Keywords:Qindaparticles,lipopolysaccharides,microglialcells,oxidativestressresponse,p38MAPK,Nrf2,HO-1Oxidativestressresponsesinmicroglialcellsplayanessentialroleinvariousneurodegenerativediseases,includingAlzheimer'sdisease,Parkinson'sdisease,andmultiplesclerosis.Therefore,identifyingnewtherapeuticagentsthatcanalleviateoxidativestressinmicroglialcellshasbecomecrucialforthetreatmentofthesediseases.Inthisstudy,weinvestigatedthepotentialprotectiveeffectsofQindaparticlesonLPS-inducedoxidativestressinmicroglialcells.

OurresultsshowedthatQindaparticlescouldinhibitthesecretionofTNF-αandIL-1βinducedbyLPS,suggestingthatQindaparticleshaveanti-inflammatoryproperties.Moreover,QindaparticlesincreasedtheexpressionofNrf2andHO-1inBV2cellsinducedbyLPS.TheactivationofNrf2/HO-1signalingpathwayisknowntoplayanessentialroleinthecellulardefenseagainstoxidativestress.Therefore,theupregulationofNrf2/HO-1expressionbyQindaparticlescouldindicateitspotentialantioxidanteffects.

Further,wefoundthatQindaparticlescouldregulatethephosphorylationofp38MAPKinducedbyLPS.Thep38MAPKpathwayisinvolvedintheregulationofvariouscellularprocesses,includinginflammationandoxidativestress.Therefore,theinhibitionofp38MAPKphosphorylationbyQindaparticlescouldfurthersuggestitsanti-inflammatoryandantioxidanteffects.

Overall,ourfindingssuggestthatQindaparticlescouldalleviateLPS-inducedoxidativestressresponsesthroughtheregulationofp38MAPK/Nrf2/HO-1signalpathwayinmicroglialcells.TheseresultsindicatethepotentialtherapeuticvalueofQindaparticlesinthetreatmentofneurodegenerativediseasesassociatedwithoxidativestressandinflammationInadditiontothepotentialtherapeuticeffectsdiscussedabove,Qindaparticleshavealsobeenshowntohaveotherpromisingqualitiesforuseinclinicalsettings.Forexample,Qindaparticleshavebeenshowntohaveexcellentbiocompatibilityinvitro,suggestingthattheymaybewell-toleratedinlivingorganisms(Yangetal.,2019).Furthermore,sinceQindaparticlesarederivedfromnaturalingredients,theyarelesslikelytocauseadverseeffectswhencomparedtosyntheticdrugsthatmayhavetoxicorharmfulconstituents.

AnothernoteworthyaspectofQindaparticlesisthattheyhavedemonstratedgoodstabilityovertime,maintainingtheirantioxidantandanti-inflammatoryeffectswhenstoredforextendedperiods(Zhouetal.,2017).Thischaracteristicisimportantforthedevelopmentofpharmaceuticalsandnutraceuticals,asitallowsforlong-termstorageandtransportationwithoutareductioninefficacy.

Finally,Qindaparticleshavealsobeenfoundtohavepotentialantibacterialproperties.AstudyconductedbyYaoetal.(2020)demonstratedthatQindaparticleswerehighlyeffectiveininhibitingthegrowthofthreestrainsofbacteriacommonlyfoundinwoundinfections.ThisfindinghighlightsthepotentialuseofQindaparticlesasatopicaltreatmentforbacterialinfections.

Inconclusion,Qindaparticleshaveshownsignificantpotentialasatherapeuticagentforthetreatmentofneurodegenerativediseasesassociatedwithoxidativestressandinflammation.Throughtheregulationofthep38MAPK/Nrf2/HO-1signalingpathway,Qindaparticleshavedemonstratedantioxidantandanti-inflammatoryeffectsinmicroglialcells.Inadditiontotheirpotentialtherapeuticbenefits,Qindaparticleshaveexcellentbiocompatibility,goodstability,andpromisingantibacterialproperties.FurtherresearchisneededtofullyexplorethetherapeuticpotentialofQindaparticlesandtheirmechanismsofactionindifferentdiseasestatesInadditiontotheiruseintraditionalmedicine,nanoparticleshaveshownpotentialforuseinvariousfields,includingdrugdelivery,imaging,anddiagnosis.Theabilityofnanoparticlestotargetspecificcellsandtissues,aswellastheirhighsurfacearea-to-volumeratio,makesthemattractivecandidatesfordrugdeliverysystems.Qindaparticles,forexample,haveshownpromisingresultsinthetreatmentofvariousdiseasesthroughtheregulationofdifferentsignalingpathways.

Apartfromtheirtherapeuticpotential,Qindaparticleshavealsodemonstratedexcellentbiocompatibilityandstability.Biocompatibilityreferstotheabilityofamaterialtointeractwithbiologicalsystemswithoutcausingadverseeffects.InthecaseofQindaparticles,theyarewell-toleratedbycellsandhaveminimaltoxicity.Thisisacrucialfactorfortheirpotentialuseinmedicine.

Stabilityisanotheressentialcharacteristicofnanoparticles.Stabilityreferstotheabilityofamaterialtomaintainitsphysicalandchemicalpropertiesovertime.Nanoparticlescanbeunstableduetovariousfactors,suchastemperature,pH,orexposuretolight.Qindaparticleshavedemonstratedgoodstability,whichisaprerequisitefortheirpotentialuseinpharmaceuticalandbiomedicalapplications.

AnotherpotentialapplicationofQindaparticlesisinantibacterialtherapies.Inrecentyears,theemergenceofantibiotic-resistantbacteriahasbecomeasignificantchallengeforthetreatmentofinfectiousdiseases.Nanoparticles,includingQindaparticles,haveshownantibacterialpropertiesagainstvarioustypesofbacteria.However,furtherresearchisneededtofullyunderstandtheantibacterialmechanismsofQindaparticlesandtheirpotentialforuseinclinicalsettings.

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