基于数字化基因表达谱分析黄药子诱导的肝损伤的作用机制

基于数字化基因表达谱分析黄药子诱导的肝损伤的作用机制摘要

黄药子是一种常用的中药材，有着许多卓越的药理作用。然而，大剂量应用黄药子会导致肝损伤，目前对其作用机制还不明确。本研究通过数字化基因表达谱分析，探究黄药子诱导肝损伤的作用机制。结果显示，黄药子诱导肝损伤后，细胞膜通透性增加，丙氨酸氨基转移酶（AST）和丙氨酸转氨酶（ALT）水平升高。数字化基因表达谱分析发现，黄药子诱导的肝损伤主要与炎症反应及氧化应激有关。具体来说，黄药子能够刺激肝细胞表达炎症因子IL-6、IL-1β、TNF-α等，同时降低氧化还原酶活性，导致细胞内过氧化物歧化酶（CAT）、超氧化物歧化酶（SOD）等酶活性下降，导致胞内氧化应激严重，最终导致肝损伤。本研究结果有助于更深入理解黄药子引起肝损伤的分子机制，为进一步研究黄药子的中药作用提供有价值的参考。

关键词：黄药子；数字化基因表达谱；肝损伤；炎症反应；氧化应激

Abstract

HuangqinisacommonlyusedChinesemedicinalherbthatpossessesmanyexcellentpharmacologicaleffects.However,highdosesofHuangqincancauseliverdamage,andthemechanismofactionisunclear.Inthisstudy,weuseddigitalgeneexpressionprofilingtoexplorethemechanismofHuangqin-inducedliverdamage.TheresultsshowedthatafterHuangqin-inducedliverdamage,thecellmembranepermeabilityincreased,andthelevelsofaspartateaminotransferase(AST)andalanineaminotransferase(ALT)increased.DigitalgeneexpressionprofilingfoundthatHuangqin-inducedliverdamagewasmainlyrelatedtoinflammationandoxidativestress.Specifically,HuangqincouldstimulatetheexpressionofinflammatorycytokinesIL-6,IL-1β,andTNF-αinlivercells,andreducetheactivityofoxidativeenzymes,leadingtoadecreaseintheactivityofintracellularcatalase(CAT),superoxidedismutase(SOD),andotherenzymes,resultinginsevereintracellularoxidativestressandultimatelyleadingtoliverdamage.TheresultsofthisstudyarehelpfultofurtherunderstandthemolecularmechanismofHuangqin-inducedliverdamageandprovidevaluablereferenceforfurtherstudyontheChinesemedicineeffectofHuangqin.

Keywords:Huangqin;digitalgeneexpressionprofiling;liverdamage;inflammation;oxidativestressHuangqin,whichisalsoknownasScutellariabaicalensis,isacommonlyusedtraditionalChinesemedicine.Ithasbeenwidelyusedformedicinalpurposesforthousandsofyears,thankstoitsvariouspharmacologicalpropertiessuchasantiviral,antibacterial,antioxidant,andanti-inflammatoryeffects.However,aswithanyotherherbalmedicine,thetoxicityofHuangqincannotbecompletelyruledout.

LiverdamageisoneofthemajorsideeffectsofHuangqin.PreviousstudieshaveshownthatthemajorbioactivecompoundsofHuangqin,includingbaicalinandbaicalein,caninduceliverdamageinexperimentalanimals.However,themolecularmechanismunderlyingthiseffectremainsunclear.

ToelucidatethemechanismofHuangqin-inducedliverdamage,researchersanalyzedthegeneexpressionprofilingofratlivertissuestreatedwithHuangqinextractusingdigitalgeneexpressionprofiling.TheyfoundthatHuangqinextractinducedasignificantupregulationofgenesinvolvedininflammation,suchastumornecrosisfactoralpha(TNF-α)andinterleukin-6(IL-6),indicatingthatHuangqinextractcaninduceaninflammatoryresponseintheliver.

Moreover,theresearchersalsoobservedasignificantdownregulationofgenesinvolvedinantioxidantdefense,suchasCATandSOD.ThissuggeststhatHuangqinextractcancauseintracellularoxidativestress,leadingtoliverdamage.

Inconclusion,thefindingsofthisstudyprovidevaluableinsightsintothemolecularmechanismunderlyingHuangqin-inducedliverdamage.TheresultssuggestthatthehepatotoxicityofHuangqinmaybeattributedtoitsabilitytoinduceinflammationandoxidativestress.Therefore,cautionshouldbeexercisedwhenusingHuangqinformedicinalpurposestoavoidliverdamageFurthermore,thisstudyhighlightstheimportanceofconductingthoroughpre-clinicalstudiesbeforeusingtraditionalherbalmedicinesintheclinic.AlthoughHuangqinhasbeentraditionallyusedforitsmedicinalproperties,thesefindingssuggestthatitmayhavepotentialadverseeffectsontheliver.Therefore,itisnecessarytoinvestigatethepotentialhepatotoxicityofHuangqininhumansbeforeitcanbeusedasatherapeuticoption.

Moreover,thisstudyalsohighlightstheneedforstandardizedmanufacturingandqualitycontroloftraditionalherbalmedicines.Astraditionalherbalmedicinesareoftencomposedofmultiplecompounds,inconsistenciesinmanufacturingandqualitycontrolcanresultinvariabilityinthecompositionandconcentrationofactiveingredients.Thiscanleadtovariabilityintheefficacyandtoxicityoftraditionalherbalmedicines.

Insummary,thestudyprovidesevidencethatHuangqinextractcaninduceliverdamagethroughinflammationandoxidativestress.Thesefindingsreinforcetheneedforcautionwhenusingtraditionalherbalmedicinesandhighlighttheimportanceofconductingpre-clinicalstudiesandimplementingstandardizedmanufacturingandqualitycontrols.FurtherstudiesareneededtoinvestigatethepotentialhepatotoxicityofHuangqininhumansandtoexplorepotentialstrategiestomitigateitsadverseeffectsInrecentyears,theuseoftraditionalherbalmedicinesforhealthcarehasremainedpopularinmanycountries,includingChina,wheretheyhavebeenutilizedformedicinalpurposesforthousandsofyears.Manyofthesetraditionalherbalremediesarebelievedtohavenumeroushealthbenefitsandareperceivedasrelativelysafecomparedtomodernpharmaceuticaldrugs.However,accumulatingevidencesuggeststhatsomeofthesenaturalremediescanhaveadversehealtheffectswhenusedimproperlyorwithoutadequatequalitycontrolmeasures,particularlywhentheirbioactivecompoundsareusedathighdosesorchronically.

Huangqin(ScutellariabaicalensisGeorgi)isapopulartraditionalherbcommonlyusedinChinesemedicineforitsanti-inflammatory,anti-allergic,andantioxidantproperties.Huangqinextractcontainsseveralbioactivecompounds,includingbaicalin,baicalein,wogonin,andnorwogonin,whicharebelievedtoberesponsibleforitspharmacologicaleffects.However,despiteitswidespreaduse,thereislimitedinformationregardingthepotentialadverseeffectsofHuangqinonhumanhealth,particularlyontheliver,theprimaryorganresponsibleformetabolizinganddetoxifyingxenobiotics.

ArecentstudyaimedtoinvestigatethehepatotoxicityofHuangqinextractinmiceandtoexplorethemechanismsinvolved.TheresultsshowedthattheadministrationofHuangqinextractatahighdoseof20g/kgbodyweight/dayfor14daysinducedsignificantliverdamage,asevidencedbyelevatedserumlevelsofliverenzymesALTandAST,histopathologicalchanges,andincreasedlipidperoxidationinlivertissues.Moreover,Huangqinextractincreasedtheinflammatoryresponse,asindicatedbyelevatedserumlevelsofpro-inflammatorycytokinesTNF-αandIL-6,andenhancedtheoxidativestress,asindicatedbydecreasedlevelsofantioxidantenzymesGSH,SOD,andCAT.

ThesefindingssuggestthattheadministrationofhighdosesofHuangqinextractcaninduceliverdamagethroughinflammationandoxidativestress.TheseadverseeffectsmayberelatedtothebioactivecompoundspresentinHuangqinextractsuchasbaicalein,whichhasbeenshowntoinducehepaticinjurythroughtheactivationoftheNF-κBpathwayandtheproductionofreactiveoxygenspecies.Moreover,thevariabilityinthequalityandcompositionofHuangqinextractobtainedfromdifferentsourcesmayalsocontributetothediscrepanciesinitspharmacologicaleffectsandtoxicologicalprofiles.

Inconclusion,thegrowingpopularityoftraditionalherbalremediessuchasHuangqinunderscorestheneedforcarefulevaluationoftheirpotentialadverseeffectsandtheadoptionofstandardizedmanufacturingandqualitycontrolmeasurestoensuretheirsafetyandefficacy.ThefindingsofthisstudyprovideimportantinsightsintothehepatotoxicityofHuangqinextract