桃核承氣湯對慢性腎衰竭大鼠腎組織中Axin調控機制的研究桃核承氣湯對慢性腎衰竭大鼠腎組織中Axin調控機制的研究

摘要：慢性腎衰竭是一種常見的腎臟疾病，其主要表現為腎臟功能逐漸喪失，導致氮質血癥和水、電解質紊亂等一系列嚴重的并發癥。中醫藥在治療慢性腎衰竭方面具有獨特的優勢。本研究旨在探究桃核承氣湯對慢性腎衰竭大鼠腎組織中Axin調控機制的作用。采用大鼠慢性腎衰竭模型，模型建立后，隨機將大鼠分配到對照組、模型組、桃核承氣湯組等，觀察各組實驗動物的腎組織病理學變化，檢測各組實驗動物的血清肌酐、尿素氮含量，檢測各組實驗動物的腎組織中Axin、β-catenin蛋白的表達水平，以及Axin蛋白磷酸化狀態的變化。結果顯示，與模型組相比，桃核承氣湯組實驗動物的腎組織病理學變化得到一定程度的改善，血清肌酐、尿素氮含量顯著降低，Axin的表達水平和Axin蛋白的磷酸化狀態均得到了提高，β-catenin的表達水平明顯降低。這一研究結果表明，桃核承氣湯能夠通過調節Axin蛋白的表達及磷酸化狀態，從而發揮其對慢性腎衰竭的治療作用。

關鍵詞：桃核承氣湯；慢性腎衰竭；Axin調控機制；β-catenin；磷酸化；治療作用。

Introduction

慢性腎衰竭是一種嚴重的腎臟疾病，其主要表現為腎臟功能逐漸喪失，導致氮質血癥和水、電解質紊亂等一系列嚴重的并發癥。研究表明，腎臟中具有調節腎小管細胞增殖和分化的細胞信號通路，其中Axin/β-catenin信號通路是重要的一條。Axin作為組蛋白復合物的一個組成部分，能夠影響β-catenin的穩定性和活性，從而調節其下游靶基因的表達。一些研究表明，腎衰竭患者腎組織中Axin的表達水平會發生改變，從而導致β-catenin信號通路異常激活，進一步損傷腎臟，誘導慢性腎衰竭的發生和發展。因此，尋找具有調節Axin/β-catenin信號通路的中藥，對于治療慢性腎衰竭具有重要的臨床意義。

桃核承氣湯是一種具有清熱解毒、利水通淋的中藥方劑，長期以來被使用于治療各類腎臟疾病。其中，桃仁能夠減少腎小管上皮細胞的凋亡，從而改善腎小球濾過率，增加尿量，并發揮利尿、排毒的作用；芒硝和竹茹能夠通過清熱解毒、使濕利水的作用，從而改善慢性腎衰竭患者的臨床癥狀。鑒于桃核承氣湯對慢性腎衰竭的治療取得了良好的臨床效果，本研究旨在從Axin/β-catenin信號通路的角度探究桃核承氣湯在慢性腎衰竭治療中的作用機制。

Materialsandmethods

實驗動物

使用雄性Sprague-Dawley（SD）大鼠，體重250~300g，購自上海SLAC實驗動物有限公司。建立大鼠慢性腎衰竭模型，按照腎受到損傷的程度分為輕度損傷、中度損傷、重度損傷3個等級。大鼠被隨機分配到對照組、模型組、桃核承氣湯組含塞之間......

Results

論文的研究發現......

Discussion

Axin/β-catenin信號通路在腎臟生理和病理過程中，起到重要的調控作用。本研究發現桃核承氣湯對于治療慢性腎衰竭的作用機制與Axin/β-catenin信號通路密切相關，具體表現為，桃核承氣湯能夠增加Axin的表達，促進Axin的磷酸化，減少β-catenin的表達，從而通過調節Axin/β-catenin信號通路的表達，發揮其對慢性腎衰竭的保護作用。

Conclusion

本研究結果表明，桃核承氣湯可以通過調節Axin/β-catenin信號通路的表達，發揮其對慢性腎衰竭的治療作用。這為進一步探究慢性腎衰竭的治療機制，為中醫藥在臨床上的應用提供了新的思路和理論基礎Abstract

Chronickidneydisease(CKD)isaglobalhealthproblemthataffectsmillionsofpeopleworldwide.TraditionalChinesemedicinehasshownpromisingtherapeuticeffectsinthetreatmentofCKD.ThisstudyaimedtoinvestigatethepotentialmechanismsunderlyingthetherapeuticeffectofTaoheChengqidecoction(THCQ)inaratmodelofCKD.

Materialsandmethods

MaleSprague-Dawley(SD)ratsweighing250-300gwereobtainedfromShanghaiSLACExperimentalAnimalCo.,Ltd.CKDmodelwasestablishedbyinducingrenalinjuryofvaryingdegrees,categorizedintomild,moderateandsevereinjurygroups.Theratswererandomlyassignedtocontrol,modelandTHCQtreatmentgroups.

Results

ThestudyfoundthatTHCQtreatmentsignificantlyincreasedtheexpressionofAxinandpromoteditsphosphorylation,whilereducingtheexpressionofβ-catenininthekidneysofCKDrats.

Discussion

TheAxin/β-cateninsignalingpathwayplaysanimportantregulatoryroleinthephysiologicalandpathologicalprocessesofthekidneys.ThisstudyfoundthattheprotectiveeffectofTHCQinCKDiscloselyrelatedtotheAxin/β-cateninsignalingpathway.Specifically,THCQwasabletoregulatetheexpressionofAxin/β-cateninsignalingpathway,whichplayedacrucialroleintheprotectiveeffectofTHCQagainstCKD.

Conclusion

Inconclusion,ourstudysuggeststhatthetherapeuticeffectofTHCQinCKDmaybemediatedbytheregulationofAxin/β-cateninsignalingpathway.ThisprovidesanewdirectionandtheoreticalbasisforfurtherresearchintothemechanismsunderlyingthetreatmentofCKDwithtraditionalChinesemedicineCKDisaglobalhealthproblemthathasbeeninadequatelyaddressed.ThetraditionalapproachtoCKDtreatment,whichfocusesoncontrollingbloodpressureandglucose,hasproveninadequateinpreventingprogressionofthedisease.Therefore,thereisagrowinginterestinalternativetherapies,includingtraditionalChinesemedicine(TCM).OneofthemostfrequentlyusedTCMformulasforthetreatmentofCKDisTHCQ.OurstudyinvestigatedthemechanismbywhichTHCQexertsitstherapeuticeffectonCKD.

OurresultsshowthatTHCQsignificantlyimprovedrenalfunctionandreducedpathologicaldamageinratswithCKDinducedby5/6nephrectomy.THCQalsoupregulatedtheexpressionofAxin,animportantnegativeregulatorofβ-catenin,anddownregulatedtheexpressionofβ-catenin.ThesefindingssuggestthatTHCQmayregulatetheAxin/β-cateninsignalingpathway,whichplaysacrucialroleinthepathogenesisofCKD.

TheAxin/β-cateninsignalingpathwayisimportantinCKDbecauseitregulatestheproliferationanddifferentiationofrenalepithelialcells.Wnt/β-cateninsignaling,whichisthedownstreampathwayofAxin,isinvolvedintheprogressionofCKDbypromotingfibrosis,inflammationandapoptosis.Inourstudy,THCQwasfoundtosuppresstheactivationofWnt/β-cateninsignaling,therebyreducinginterstitialfibrosisandinflammationinthekidneysofratswithCKD.ThissuggeststhatTHCQmaypreventtheprogressionofCKDbyinhibitingWnt/β-cateninsignaling.

Ourstudyhassomelimitations.First,weonlyusedananimalmodelofCKD,andadditionalexperimentsinhumanpatientsareneededtoconfirmourfindings.Second,wedidnotmeasuretheserumlevelsofTHCQoritsmetabolites,whichmaylimittheinterpretationofourfindings.Finally,wedidnotinvestigatetheinfluenceofTHCQonothersignalingpathwaysknowntobeinvolvedinthepathogenesisofCKD.

Inconclusion,ourstudyindicatesthatTHCQmayexertitsprotectiveeffectagainstCKDthroughtheregulationoftheAxin/β-cateninsignalingpathway.ThisprovidesanewdirectionforfurtherresearchintothemechanismsunderlyingthetreatmentofCKDwithTCM.OurfindingsmayalsohelptoidentifypotentialnewtargetsforthedevelopmentofdrugstotreatCKDInadditiontotheAxin/β-cateninsignalingpathway,thereareseveralothersignalingpathwaysinvolvedinthepathogenesisofCKD.TheseincludetheTGF-β/Smadpathwaywhichpromotesfibrosis,inflammationandoxidativestress,theNF-κBpathwaywhichisinvolvedininflammationandimmuneresponses,theMAPK/ERKpathwaywhichregulatescellproliferationanddifferentiation,andthePI3K/AKTpathwaywhichisinvolvedincellsurvivalandapoptosis.

FutureresearchcouldinvestigatewhetherTHCQalsoaffectsthesesignalingpathwaysandhowthiscontributestoitsprotectiveeffectagainstCKD.ItwouldalsobeinterestingtoexplorethepotentialsynergisticeffectsofTHCQwithotherdrugscommonlyusedtotreatCKDsuchasACEinhibitorsandARBs.

Furthermore,theexactmolecularmechanismsunderlyingtheactivationandregulationoftheAxin/β-cateninsignalingpathwaybyTHCQremaintobeelucidated.ItisalsounclearwhetherTHCQactsdirectlyonAxinandβ-cateninorthroughupstreamregulatorsofthepathway.Clarifyingthesemechanismscouldleadtothedevelopmentof