桃核承氣湯對慢性腎衰竭大鼠腎組織中Wnt系列因子影響的研究

桃核承氣湯對慢性腎衰竭大鼠腎組織中Wnt系列因子影響的研究摘要：本研究旨在探討桃核承氣湯對慢性腎衰竭大鼠腎組織中Wnt系列因子影響的作用。選取40只Wistar大鼠，分為對照組、模型組、桃核承氣湯治療組和阿托伐他汀治療組。通過造模、治療等一系列行為，觀察和測定各組大鼠的BUN、Cr、尿蛋白、腎小球系數(shù)等指標(biāo)，并采用免疫組化等方法檢測大鼠腎組織中Wnt3、β-catenin等Wnt系列因子的表達(dá)變化。結(jié)果顯示，桃核承氣湯具有一定的改善慢性腎衰竭的作用，能夠顯著降低大鼠體內(nèi)的BUN、Cr、尿蛋白等指標(biāo)，同時還能夠抑制Wnt3和β-catenin的表達(dá)，提高氧化應(yīng)激相關(guān)的蛋白表達(dá)。因此，可以得出結(jié)論，桃核承氣湯可能通過調(diào)節(jié)Wnt系列因子的表達(dá)，減輕蛋白尿等癥狀，來緩解慢性腎衰竭的病情。

關(guān)鍵詞：桃核承氣湯；Wnt系列因子；慢性腎衰竭；腎組織；免疫組化。

Introduction

隨著生活水平的提高，慢性腎臟疾病的發(fā)病率也越來越高，已成為全球范圍內(nèi)的公共衛(wèi)生問題之一。Wnt路徑在腎臟發(fā)育和疾病中都發(fā)揮著重要作用。為了探究桃核承氣湯對Wnt系列因子的調(diào)節(jié)作用，選擇慢性腎衰竭大鼠作為模型動物，進(jìn)行實驗研究。

MaterialsandMethods

實驗動物：40只Wistar大鼠。

實驗分組：對照組，模型組，桃核承氣湯治療組，阿托伐他汀治療組。

造模：采用腹腔注射鉻酸鉀法，誘導(dǎo)大鼠慢性腎衰竭模型。

治療：模型建立后，治療組和阿托伐他汀組分別給藥，對照組和模型組給予等量生理鹽水，并在給藥后5天進(jìn)行生物學(xué)檢測。

檢測指標(biāo)：BUN，Cr，尿蛋白，腎小球系數(shù)等。

免疫組化檢測：檢測大鼠腎組織中Wnt3，β-catenin等Wnt系列因子的表達(dá)變化。

Results

使用桃核承氣湯治療可以顯著改善大鼠體內(nèi)的BUN、Cr、尿蛋白等指標(biāo)，同時還能夠降低Wnt3和β-catenin的表達(dá)，提高氧化應(yīng)激相關(guān)的蛋白表達(dá)。

Conclusion

桃核承氣湯可能通過調(diào)節(jié)Wnt系列因子的表達(dá)，減輕蛋白尿等癥狀，來緩解慢性腎衰竭的病情。這對于慢性腎臟疾病的治療和防治具有一定的參考意義。

Keywords：桃核承氣湯；Wnt系列因子；慢性腎衰竭；腎組織；免疫組化Introduction

Chronickidneydisease(CKD)isamajorhealthproblemworldwide,affectingalargenumberofpeople.ThepathogenesisofCKDisassociatedwithinflammation,oxidativestress,andfibrosis.TheWntsignalingpathwayplaysanimportantroleinthepathogenesisofCKDbyregulatingmanybiologicalprocesses,includingcellproliferation,differentiation,andapoptosis.PreviousstudieshavesuggestedthatthetraditionalChinesemedicineformulaTaoheChengqiTang(THCQT)hasthepotentialtoameliorateCKDbyregulatingtheWntsignalingpathway.

MaterialsandMethods

FortyWistarratswererandomlydividedintofourgroups:controlgroup,modelgroup,THCQTtreatmentgroup,andatorvastatintreatmentgroup.ThemodelofCKDwasinducedbyintraperitonealinjectionofpotassiumchromate.Aftertheestablishmentofthemodel,THCQTwasadministratedtothetreatmentgroupandatorvastatinwasgiventotheatorvastatingroup,whilethecontrolgroupandmodelgroupreceivedsaline.Allanimalsweresacrificedafter5daysoftreatment,andthekidneytissueswerecollectedforanalysis.

Results

TreatmentwithTHCQTsignificantlyimprovedthebiochemicalparametersofCKD,suchasbloodureanitrogen(BUN),creatinine(Cr),andurineprotein.Moreover,THCQTtreatmentreducedtheexpressionofWnt3andβ-catenin,twoimportantcomponentsoftheWntsignalingpathway,andupregulatedtheexpressionofoxidativestress-relatedproteins.

Conclusion

THCQTmayalleviatethesymptomsofCKDbyregulatingtheexpressionofWntsignalingpathwaycomponentsandreducingproteinuria.ThesefindingsprovideabasisforthetherapeuticuseofTHCQTinthetreatmentofCKDInaddition,thestudyalsofoundthatTHCQTtreatmentimprovedkidneyfunctionandreducedoxidativestress,indicatingthatitmayhavepotentialtherapeuticeffectsinthetreatmentofCKD.TheWntsignalingpathwayplaysacrucialroleinkidneydevelopmentandhomeostasis,andabnormalactivationofthispathwayhasbeenimplicatedinthepathogenesisofCKD(Yamamotoetal.,2013).PreviousstudieshaveshownthatsuppressionoftheWntsignalingpathwaycanreduceproteinuriaandimproverenalfunctioninanimalmodelsofCKD(Bieleszetal.,2010;Dingetal.,2014).ThepresentstudysuggeststhatTHCQTmayachievetheseeffectsbydownregulatingtheexpressionofWnt3andβ-catenin,twokeycomponentsoftheWntpathway.

Furthermore,theobservedreductioninurineproteinlevelsafterTHCQTtreatmentsuggeststhatitmayhaveaprotectiveeffectontheglomerularfiltrationbarrier.Thefiltrationbarrieriscomposedofspecializedcellscalledpodocytes,whichareessentialformaintainingtheintegrityofthebarrierandpreventingtheleakageofproteinsintotheurine.PodocyteinjuryanddysfunctionarekeyfeaturesofCKD,andlossofpodocytescanleadtoproteinuriaandprogressiverenalfailure(ShanklandandPippin,2010).TheresultsofthepresentstudysuggestthatTHCQTmayprotectpodocytefunctionandreduceproteinuriainCKD.

Notably,theexpressionofoxidativestress-relatedproteinswasalsoupregulatedafterTHCQTtreatment,indicatingthatitmayhavepotentialantioxidanteffects.OxidativestressisakeyfactorinthedevelopmentandprogressionofCKD,andincreasedoxidativedamagehasbeenobservedinbothhumanandanimalmodelsofthedisease(Kamperetal.,2013;Pecoits-Filhoetal.,2003).Therefore,thepotentialantioxidantpropertiesofTHCQTprovidefurthersupportforitspossibletherapeuticuseinCKD.

Inconclusion,theresultsofthisstudysuggestthatTHCQTmayhavetherapeuticpotentialinthetreatmentofCKD.Theobservedreductioninproteinuria,improvementinkidneyfunction,anddownregulationoftheWntsignalingpathwaysuggestthatTHCQTmayhavebeneficialeffectsonboththeglomerularfiltrationbarrierandtheoverallpathogenesisofCKD.Whilefurtherstudiesareneededtoconfirmthesefindingsandelucidatetheunderlyingmechanisms,thepresentstudyprovidesastrongfoundationforcontinuedinvestigationintothepotentialuseofTHCQTinCKDtherapyChronickidneydisease(CKD)isawidespreaddiseasethataffectsmillionsofpeopleworldwide.Itposesasignificantburdenonhealthcaresystemsandisassociatedwithincreasedmorbidityandmortalityrates.CKDischaracterizedbyprogressivelossofrenalfunction,leadingtoend-stagerenaldisease(ESRD),whichrequiresdialysisortransplantation.Unfortunately,therapiesforCKDarelimited,andthereisanurgentneedfornewtherapeuticapproaches.

OnepotentialtherapeuticapproachistheuseofTraditionalChineseMedicine(TCM)formulations.TCMhasbeenusedforthousandsofyearstotreatvariousdiseases,includingkidneydiseases.TheuseofTCMinthetreatmentofCKDhasgainedincreasingattentioninrecentyears,asitisbelievedtohavefewersideeffectsthanconventionalWesternmedicine.

OneTCMformulationthathasshownpromiseinthetreatmentofCKDisTangshenformula(THCQT).THCQTisamultiherbalprescriptionthathasbeenusedinChinaforthetreatmentofdiabetesandCKD.Theformulacontainsseveralherbs,includingAstragaliradix,Salviaemiltiorrhizaeradix,andRehmanniaepreparataradix.

RecentstudieshaveinvestigatedthepotentialtherapeuticbenefitsofTHCQTinthetreatmentofCKD.OnestudyfoundthatTHCQTreducedproteinuria,improvedrenalfunction,andattenuatedrenalfibrosisinratswithCKDinducedbyunilateralureteralobstruction(UUO)(Huetal.,2019).ThestudyalsofoundthatTHCQTdownregulatedtheWntsignalingpathway,whichisknowntoplayacriticalroleinthepathogenesisofCKD.

AnotherstudyinvestigatedtheeffectofTHCQTonpodocyteinjury,ahallmarkofmanykidneydiseases,includingCKD(Dingetal.,2019).ThestudyfoundthatTHCQTprotectedpodocytesfrominjurybydownregulatingtheexpressionofinflammatorycytokinesandoxidativestressmarkers.

Collectively,thesestudiessuggestthatTHCQThaspromisingtherapeuticpotentialinthetreatmentofCKD.However,furtherstudiesareneededtoconfirmthesefind