甘草瀉心湯對潰瘍性結腸炎大鼠TLR4-NF-κB炎癥信號通路的調(diào)控作用研究

甘草瀉心湯對潰瘍性結腸炎大鼠TLR4-NF-κB炎癥信號通路的調(diào)控作用研究甘草瀉心湯對潰瘍性結腸炎大鼠TLR4/NF-κB炎癥信號通路的調(diào)控作用研究

摘要

目的：本研究旨在探究甘草瀉心湯在潰瘍性結腸炎大鼠TLR4/NF-κB炎癥信號通路的調(diào)控作用。

方法：將50只SD大鼠隨機分為5組，每組10只。除了對照組外，其余四組均注射DSS誘導潰瘍性結腸炎模型。其中兩組分別灌胃甘草瀉心湯低劑量組和高劑量組，每天一次，連續(xù)給藥14天。另外兩組灌胃生理鹽水，作為溶劑對照組和模型組。給藥后，采用HE染色、WesternBlot、RT-qPCR等手段，分析了各組大鼠腸組織病理變化、TLR4/NF-κB炎癥信號通路相關蛋白表達及基因表達水平等指標。

結果：經(jīng)過14天的處理，相較于模型組和溶劑對照組，甘草瀉心湯低劑量組和高劑量組大鼠腸道病理改善明顯，炎癥程度明顯降低。同時，甘草瀉心湯高劑量組相較于低劑量組，可以更顯著地抑制TLR4、NF-κB、TNF-α、IL-6mRNA及蛋白的表達。

結論：甘草瀉心湯在潰瘍性結腸炎模型大鼠中可以明顯改善炎癥程度，可能通過抑制TLR4/NF-κB炎癥信號通路的激活發(fā)揮作用。

關鍵詞：甘草瀉心湯；潰瘍性結腸炎；TLR4/NF-κB炎癥信號通路；病理改善；抑制

Abstract

Objective:ToinvestigatetheregulatoryeffectofGancaoXieXinTangontheTLR4/NF-κBinflammatorysignalingpathwayinratswithulcerativecolitis.

Methods:FiftySDratswererandomlydividedintofivegroups,with10ratsineachgroup.Exceptforthecontrolgroup,theremainingfourgroupswereinducedwithulcerativecolitisbyintraperitonealinjectionofDSS.TwogroupsweregivenGancaoXieXinTangatlowandhighdosesbygavage,onceadayfor14consecutivedays.Theothertwogroupsweregivenphysiologicalsalineasasolventcontrolgroupandamodelgroup.Afteradministration,HEstaining,Westernblot,RT-qPCRandothermethodswereusedtoanalyzethepathologicalchangesofintestinaltissues,theexpressionandgeneexpressionlevelsofTLR4/NF-κBinflammatorysignalpathway-relatedproteinsineachgroupofrats.

Results:After14daysoftreatment,comparedwiththemodelgroupandthesolventcontrolgroup,thecolonicpathologicalimprovementofthelow-doseandhigh-dosegroupsofGancaoXieXinTangratswasobvious,andthedegreeofinflammationwassignificantlyreduced.Meanwhile,comparedwiththelowdosegroup,thehighdosegroupofGancaoXieXinTangcanmoresignificantlyinhibittheexpressionofTLR4,NF-κB,TNF-α,IL-6mRNAandprotein.

Conclusion:GancaoXieXinTangcansignificantlyimprovethedegreeofinflammationinratswithulcerativecolitis,possiblybyinhibitingtheactivationoftheTLR4/NF-κBinflammatorysignalingpathway.

Keywords:GancaoXieXinTang;ulcerativecolitis;TLR4/NF-κBinflammatorysignalingpathway;pathologicalimprovement;inhibitionUlcerativecolitis(UC)isatypeofinflammatoryboweldiseasethatcausesinflammationandulcersinthecolonandrectum.Itcancausesymptomssuchasabdominalpain,diarrhea,andrectalbleeding.CurrenttreatmentsforUCincludeanti-inflammatorydrugs,immunesystemsuppressants,andsurgery.

However,traditionalChinesemedicine(TCM)hasalsobeenusedtotreatUC.GancaoXieXinTangisaTCMformulathatconsistsofLicorice(Gancao),ginger(Shengjiang),jujube(Dazao),andpinellia(Banxia).GancaoXieXinTanghasbeenusedtotreatgastrointestinaldisorders,includingUC.

Inthisstudy,theresearchersinvestigatedtheeffectofGancaoXieXinTangonUCinrats.TheresultsshowedthatGancaoXieXinTangcouldsignificantlyimprovethedegreeofinflammationinratswithUC.TheratstreatedwithGancaoXieXinTanghadreducedlevelsofinflammationmarkersintheircolontissue.

Furthermore,theresearchersfoundthatGancaoXieXinTangcouldinhibittheTLR4/NF-κBinflammatorysignalingpathwayinratswithUC.TheTLR4/NF-κBpathwayisanimportantpathwayinvolvedintheimmuneresponseandinflammation.Inhibitionofthispathwaycanreduceinflammation.

Overall,thisstudysuggeststhatGancaoXieXinTangmaybeapotentialtherapyforUC.FurtherstudiesareneededtoconfirmthesefindingsandinvestigatethesafetyandefficacyofGancaoXieXinTanginhumansUlcerativecolitisisachronicinflammatoryboweldiseasethataffectsmillionsofpeopleworldwide.Theexactcausesofthisdiseasearenotwellunderstood,butitisbelievedtoresultfromacombinationofgeneticandenvironmentalfactors.Currently,thereisnocureforUC,andtreatmentoptionsarelimitedtomanagingthesymptoms.

TraditionalChinesemedicine(TCM)hasbeenusedforcenturiestotreatgastrointestinaldisorders,includingUC.GancaoXieXinTangisaTCMformulathathasbeenusedforthetreatmentofvariousinflammatoryconditions.Inrecentyears,researchershavebeeninterestedininvestigatingthepotentialofGancaoXieXinTangforthetreatmentofUC.

Inananimalstudy,researchersinvestigatedtheeffectsofGancaoXieXinTangonratswithUC.TheyfoundthattheratstreatedwithGancaoXieXinTanghadreducedinflammationandimprovedgutfunctioncomparedtothecontrolgroup.TheresearchersalsofoundthatGancaoXieXinTangcouldinhibittheTLR4/NF-κBinflammatorysignalingpathway,whichisanimportantpathwayinvolvedintheimmuneresponseandinflammation.

AlthoughthesefindingssuggestthatGancaoXieXinTangmaybeapotentialtherapyforUC,furtherstudiesareneededtoconfirmthesefindingsandinvestigatethesafetyandefficacyofGancaoXieXinTanginhumans.ItisimportanttonotethatTCMformulasarecomposedofmultipleherbsthatworktogethertoproducethedesiredeffect.Therefore,thesafetyandefficacyofaTCMformularelyonthequalityoftheherbsused,theexpertiseofthepractitioner,andtheindividualizedtreatmentapproach.

Inconclusion,thepotentialofTCMinthetreatmentofUCisanareaofresearchthatdeservesfurtherattention.WhileTCMhasbeenusedforcenturiestotreatgastrointestinaldisorders,scientificevidencesupportingitsefficacyinthetreatmentofUCislimited.However,thefindingsfromthisstudysuggestthatGancaoXieXinTangmayholdpromiseasapotentialtherapyforUC.FurtherstudiesareneededtoinvestigatethesafetyandefficacyofthisTCMformulainhumansAdditionally,itisimportanttonotethatTCMshouldnotbeusedasareplacementforconventionalmedicationsandcareforUC.Instead,itcanbeusedasacomplementarytherapytoreducesymptomsandimprovequalityoflife.ItiscrucialtoconsultwithaqualifiedTCMpractitionerandagastroenterologisttocreateapersonalizedtreatmentplanthatcombinesconventionalmedicineandTCM.

Furthermore,moreresearchisneededtoidentifytheactivecompoundsandmechanismsofactionofTCMformulasusedinthetreatmentofUC.ThiscanhelpelucidatehowTCMworksandpotentiallyleadtothedevelopmentofnewdrugsortherapiesforUC.

Inconclusion,althoughTCMhasbeenusedforcenturiestotreatvariousgastrointestinaldisorders,moreresearchisneededtoconfirmitsefficacyinthetreatmentofUC.ThefindingsfromthisstudysuggestthatGancaoXieXinTangmaybea