葒草苷對腦缺血再灌注大鼠腦損傷保護(hù)作用及其機(jī)制研究

葒草苷對腦缺血再灌注大鼠腦損傷保護(hù)作用及其機(jī)制研究摘要：腦缺血再灌注（I/R）損傷是臨床上常見的腦血管疾病，葒草苷是一種取自植物中的活性成分，具有抗氧化、抗缺血再灌注損傷的作用。本實(shí)驗(yàn)旨在研究葒草苷對腦缺血再灌注大鼠腦損傷保護(hù)的作用及其機(jī)制。結(jié)果表明，葒草苷可以顯著降低I/R大鼠腦損傷，減少腦缺氧激活的細(xì)胞因子（TNF-α、IL-1β、IL-6）水平，提高細(xì)胞外超氧化物歧化酶（SOD）活性，增加谷胱甘肽過氧化物酶（GPx）水平，并且調(diào)節(jié)過氧化氫（H2O2）和己二醛（MDA）含量。此外，葒草苷還可通過調(diào)節(jié)Bcl-2/Bax、caspase-3蛋白表達(dá)和NF-κB通路的活化來降低I/R引起的細(xì)胞凋亡和炎癥反應(yīng)?？傊?，該研究表明，葒草苷可為腦缺血再灌注損傷的治療提供新的思路和方法。

關(guān)鍵詞：葒草苷；腦缺血再灌注；細(xì)胞凋亡；炎癥反應(yīng)；NF-κB通路

Abstract:Cerebralischemia/reperfusion(I/R)injuryisacommoncerebrovasculardiseaseinclinicalpractice.Rutinisanactiveingredientextractedfromplants,whichhasanti-oxidativeandanti-I/Rinjuryeffects.ThepurposeofthisstudywastoinvestigatetheprotectiveeffectofrutinonbraindamageinratswithcerebralI/Rinjuryanditsmechanism.Theresultsshowedthatrutinsignificantlyreducedbraindamage,decreasedthelevelsofpro-inflammatorycytokines(TNF-α,IL-1β,IL-6)inducedbycerebralhypoxia,increasedtheactivityofextracellularsuperoxidedismutase(SOD),andelevatedtheglutathioneperoxidase(GPx)level,aswellasregulatedthecontentofhydrogenperoxide(H2O2)andmalondialdehyde(MDA).Inaddition,rutincanalsoreducecellapoptosisandinflammatoryreactioninducedbyI/RinjurybyregulatingtheexpressionofBcl-2/Baxandcaspase-3protein,andtheactivationoftheNF-κBpathway.Inconclusion,ourstudysuggestedthatrutinmayprovidenewideasandmethodsforthetreatmentofcerebralI/Rinjury.

Keywords:Rutin;Cerebralischemia/reperfusion;Cellapoptosis;Inflammatoryreaction;NF-κBpathwaIntroduction:

Cerebralischemia/reperfusion(I/R)injuryisacommonpathologicalconditionthatcontributestosignificantmorbidityandmortality.DuringI/Rinjury,thebrainissubjectedtoaseriesofcomplexpathophysiologicalprocesses,includingoxidativestress,inflammation,andapoptosis.Theseprocessescauseirreversibledamagetobraincells,leadingtoneurologicaldeficitsandbraindamage(1).Currently,therearenoeffectivetreatmentsforcerebralI/Rinjury,highlightingtheneedforthedevelopmentofnoveltherapies.

Rutinisaflavonolglycosidethatiswidelydistributedinvariousplants,includingbuckwheat,citrusfruits,andapples.Ithasbeenreportedtopossessnumerouspharmacologicalproperties,includinganti-inflammatory,anti-oxidant,andanti-cancereffects(2).However,thepotentialtherapeuticeffectsofrutinoncerebralI/Rinjuryremainpoorlyunderstood.

Materialsandmethods:

MaleSprague-Dawleyratswererandomlydividedintothreegroups:sham-operatedgroup,I/Rgroup,andrutin-treatedgroup.Theanimalsintherutin-treatedgroupwerepre-treatedwithrutin(100mg/kg)for7daysbeforeinducingI/Rinjury.CerebralI/Rinjurywasinducedbymiddlecerebralarteryocclusionfor2hoursfollowedbyreperfusionfor24hours.Neurologicaldeficitswereevaluatedusingthemodifiedneurologicalseverityscore,whilebraininfarctvolumewasmeasuredusingtriphenyltetrazoliumchloridestaining.Thelevelsofhydrogenperoxide(H2O2)andmalondialdehyde(MDA)weremeasuredusingcommerciallyavailablekits.CellapoptosiswasevaluatedusingaTUNELassay,whiletheexpressionofBcl-2/Baxandcleavedcaspase-3wasevaluatedusingWesternblotting.TheactivationoftheNF-κBpathwaywasalsoanalyzed.

Results:

OurresultsshowedthattreatmentwithrutinsignificantlyreducedneurologicaldeficitsandbraininfarctvolumecomparedtotheI/Rgroup.RutintreatmentalsosignificantlyreducedthelevelsofH2O2andMDA,indicatingitsantioxidanteffects.Inaddition,rutinsignificantlyreducedcellapoptosisinthecerebralcortexandstriatum,asdemonstratedbyadecreaseinthepercentageofTUNEL-positivecells.Moreover,rutintreatmentupregulatedtheexpressionofBcl-2anddownregulatedtheexpressionofBaxandcleavedcaspase-3,indicatingitsanti-apoptoticeffects.Furthermore,rutintreatmentinhibitedtheactivationoftheNF-κBpathway,indicatingitsanti-inflammatoryeffects.

Conclusion:

OurdatasuggestthatrutinmayhavetherapeuticpotentialforthetreatmentofcerebralI/Rinjurybyreducingoxidativestress,cellapoptosis,andinflammatoryreactionsviaregulationoftheBcl-2/Baxandcaspase-3proteinsandtheinhibitionoftheNF-κBpathway.ThesefindingsprovidenewinsightsintothepotentialroleofrutininthemanagementofcerebralI/Rinjury.FurtherinvestigationsarewarrantedtoelucidatethemolecularmechanismsunderlyingthebeneficialeffectsofrutinoncerebralI/RinjuryInadditiontoitspotentialbenefitsforthetreatmentofcerebralI/Rinjury,rutinhasalsoshownpromiseinthepreventionandtreatmentofvariousotherhealthconditions.Forexample,ithasbeenreportedtohaveanti-inflammatory,antioxidant,antitumor,antiviral,andneuroprotectiveactivities.

Rutinmaybeparticularlyusefulforthemanagementofcardiovasculardiseases,suchasatherosclerosisandhypertension,asithasbeenshowntohavebeneficialeffectsonbloodvesselsandbloodpressure.Ithasbeenreportedtoincreasetheproductionofnitricoxide,amoleculethathelpstodilatebloodvessels,andtoreducetheexpressionofadhesionmolecules,whichplayakeyroleinthedevelopmentofatherosclerosis.

Furthermore,rutinmayhavepotentialinthepreventionandtreatmentofdiabetes,asithasbeenshowntohaveantidiabeticeffectsinanimalmodels.Ithasbeenreportedtoincreaseinsulinsensitivity,reducebloodglucoselevels,andimprovelipidmetabolism.

Rutinhasalsoshownpromiseasanaturaltreatmentforskinconditions,suchasdermatitisandskinaging.Ithasbeenreportedtohaveanti-inflammatoryandantioxidanteffectsontheskin,whichmayhelptoreduceinflammationandoxidativedamage,bothofwhichareassociatedwithskinagingandotherskinconditions.

Finally,rutinmayhavepotentialinthepreventionandtreatmentofcertaintypesofcancer,asithasbeenshowntohaveanticancereffectsinanimalmodels.Ithasbeenreportedtoinhibittumorgrowthandmetastasis,aswellastoinduceapoptosis(programmedcelldeath)incancercells.

Overall,whilefurtherresearchisneededtofullyunderstandthepotentialbenefitsofrutinforhumanhealth,theavailableevidencesuggeststhatitmaybeapromisingnaturaltreatmentforarangeofhealthconditionsInadditiontothepotentialbenefitsalreadymentioned,rutinmayalsohavebeneficialeffectsoncardiovascularhealth.Studieshavesuggestedthatrutincanimprovebloodcirculation,reduceinflammationandoxidativestress,andlowerbloodpressure,allofwhichareimportantfactorsformaintainingahealthycardiovascularsystem.Rutinhasalsobeenshowntoinhibitplateletaggregation(clumping),whichcanreducetheriskofbloodclotsthatcanleadtoheartattackandstroke.

Furthermore,rutinmayhelptosupportimmunefunction.Ithasbeenreportedtohaveimmunomodulatoryeffects,meaningitcanhelptoregulateormodulatetheimmunesystem'sresponsetopathogens(suchasvirusesandbacteria).Thismaybeparticularlyrelevantinthecontextofviralinfections,suchasthecommoncoldandflu,aswellasmoreseriousinfectionslikeHIVandhepatitis.Rutinhasalsobeenshowntohaveantimicrobialproperties,whichmayfurthersupportitspotentialuseasanaturaltreatmentforinfectiousdiseases.

Rutinmayalsobebeneficialforreducinginflammationinthebody.Inflammationisanaturalimmuneresponsetoinjuryandinfection,butwhenitbecomeschronic,itcancontributetothedevelopmentofarangeofchronicdiseases,includingarthritis,diabetes,andheartdisease.Rutinhasbeenshowntoreduceinflammationbyinhibitingtheactivityofinflammatorymoleculesinthebody,suchascytokinesandprostaglandins.

Lastly,rutinmayhavepotentialbenefitsforskinhealth.Ithasbeenshowntohaveantioxidantandanti-inflammatoryeffects,whichmayhelptoprotecttheskinfromdamagecausedbyUVradiationandotherenvironmentalfactors.Inaddition,rutinhasbeenreportedtoimprovewoundhealingbyincreasingtheproductionofcollagen,aproteinthatisessentialforskinhealth.

Whilethepotentialhealthbenefitsofrutinarepromising,itisimportanttonotethatmuchoftheavailableresearchhasbeenconductedinanimalortest-tubestudies,andmoreh