電針膝眼穴調(diào)控RhoA-ROCK信號通路抑制膝骨性關(guān)節(jié)炎軟骨退變的機(jī)制研究

電針膝眼穴調(diào)控RhoA-ROCK信號通路抑制膝骨性關(guān)節(jié)炎軟骨退變的機(jī)制研究摘要

目的：本研究旨在探討電針膝眼穴對膝骨性關(guān)節(jié)炎軟骨退變的影響及其調(diào)控RhoA/ROCK信號通路的機(jī)制。

方法：建立膝骨性關(guān)節(jié)炎大鼠模型，采用電針膝眼穴干預(yù)，觀察軟骨形態(tài)學(xué)及病理變化，檢測炎性因子和RhoA/ROCK通路相關(guān)蛋白的表達(dá)。

結(jié)果：電針膝眼穴治療可明顯減緩膝骨性關(guān)節(jié)炎大鼠軟骨退變，并抑制IL-1β、TNF-α等炎性因子的表達(dá)。電針膝眼穴治療后，RhoA/ROCK信號通路中RhoA、ROCK1和ROCK2的表達(dá)均顯著下調(diào)。

結(jié)論：電針膝眼穴可以通過抑制炎癥反應(yīng)及調(diào)節(jié)RhoA/ROCK信號通路抑制膝骨性關(guān)節(jié)炎軟骨退變，為其臨床應(yīng)用提供理論基礎(chǔ)。

關(guān)鍵詞：電針膝眼穴；膝骨性關(guān)節(jié)炎；軟骨退變；炎性因子；RhoA/ROCK信號通路

Abstract

Objective:Thepresentstudyaimstoinvestigatetheeffectofelectroacupuncture(EA)onthearticularcartilagedegenerationofkneeosteoarthritis(KOA)ratsanditsmechanismofregulatingtheRhoA/ROCKsignalingpathway.

Methods:AKOAratmodelwasestablished,andEAwasappliedtothekneeeyeacupoint.Themorphologicalandpathologicalchangesofthecartilagewereobserved,andtheexpressionofinflammatoryfactorsandRhoA/ROCKpathway-relatedproteinswasdetected.

Results:TreatmentwithEAatthekneeeyeacupointcouldsignificantlyalleviatethecartilagedegenerationofKOAratsandinhibittheexpressionofinflammatoryfactorssuchasIL-1βandTNF-α.AftertheEAtreatment,theexpressionofRhoA,ROCK1,andROCK2intheRhoA/ROCKsignalingpathwaywassignificantlydownregulated.

Conclusion:EAatthekneeeyeacupointcouldinhibitthearticularcartilagedegenerationofKOAbysuppressingtheinflammatoryresponseandregulatingtheRhoA/ROCKsignalingpathway,providingatheoreticalbasisforitsclinicalapplication.

Keywords:electroacupuncture;kneeeyeacupoint;kneeosteoarthritis;cartilagedegeneration;inflammatoryfactors;RhoA/ROCKsignalingpathwaIntroduction:

Kneeosteoarthritis(KOA)isacommonchronicdegenerativejointdiseasecharacterizedbycartilagedegeneration,synovialinflammation,andboneremodeling.ThepathogenesisofKOAisrelatedtomultiplefactors,suchasaging,geneticpredisposition,andmechanicalstress.CurrenttreatmentoptionsforKOA,suchasnonsteroidalanti-inflammatorydrugs(NSDs),disease-modifyingosteoarthritisdrugs(DMOADs),andjointreplacementsurgery,havelimitations,suchasadverseeffects,highcost,andinvasiveprocedures.Therefore,thereisaneedforalternativetreatmentsthatareeffective,safe,andnoninvasive.

Electroacupuncture(EA)isaformofacupuncturethatinvolvestheapplicationofelectricalstimulationtoacupuncturepoints.EAhasbeenusedtotreatvariousmusculoskeletaldisorders,includingKOA,withpromisingresults.However,themechanismunderlyingthetherapeuticeffectofEAonKOAremainsunclear.

Methods:

Inthisstudy,weinvestigatedthetherapeuticeffectofEAatthekneeeyeacupointonarticularcartilagedegenerationinaratmodelofKOAinducedbyanteriorcruciateligamenttransection(ACLT).Theratsweredividedintofourgroups:thecontrolgroup,theKOAgroup,theEAgroup,andtheshamEAgroup.TheEAgroupreceivedEAatthekneeeyeacupointtwiceaweekfor4weeks,whiletheshamEAgroupreceivedEAatanon-acupoint.ThecontrolgroupandtheKOAgroupreceivednointervention.

Results:

OurresultsshowedthatEAatthekneeeyeacupointsignificantlyimprovedthehistologicalscoreofthearticularcartilageandreducedtheexpressionofinflammatoryfactors,suchasinterleukin-1β(IL-1β)andtumornecrosisfactor-α(TNF-α),inthesynovialmembraneandcartilageoftheKOArats.Furthermore,theexpressionofRhoA,ROCK1,andROCK2intheRhoA/ROCKsignalingpathwaywassignificantlydownregulatedintheEAgroupcomparedtotheKOAgroup.

Conclusion:

OurfindingssuggestthatEAatthekneeeyeacupointcouldinhibitthearticularcartilagedegenerationofKOAbysuppressingtheinflammatoryresponseandregulatingtheRhoA/ROCKsignalingpathway.TheseresultsprovideatheoreticalbasisfortheclinicalapplicationofEAinthetreatmentofKOAInadditiontotheabovefindings,previousstudieshavealsoreportedthepotentialmechanismsofEAinthetreatmentofKOA.Forinstance,EAattheST36andGB34acupointshasbeenfoundtoalleviatesynovitisandcartilagedamageinKOAratsbyregulatingthePI3K/Akt/mTorpathway(Chenetal.,2020).AnotherstudyshowedthatEAattheLI11andST36acupointsincreasedtheexpressionofSirt1,therebyreducinginflammationandoxidativestressinKOAmice(Zhaoetal.,2020).Furthermore,EAattheGB34acupointwasfoundtoenhancethematurationofchondrocytesandimprovearticularcartilagedefectsinarabbitmodelofKOA(Lietal.,2021).

Despitethepromisingresultsofthesestudies,somelimitationsneedtobeaddressed.Firstly,theoptimalacupointselectionandstimulationparametersofEAforthetreatmentofKOAremainunclear.DifferentacupointsandstimulationparametersmayhavedifferenttherapeuticeffectsonKOA,andastandardizedprotocolisneededforclinicalapplication.Secondly,thelong-termefficacyandsafetyofEAintreatingKOAstillneedtobefurtherinvestigated.Long-termfollow-upstudiesandsystematicreviewsarerequiredtoevaluatethepotentialadverseeffectsandbenefitsofEAforKOA.Lastly,theunderlyingmolecularmechanismsofEAinthetreatmentofKOAneedtobeelucidated.FurtherstudiesareneededtoexploretheprecisesignalingpathwaysandmoleculartargetsofEAinthemodulationofinflammation,oxidativestress,andchondrocytemetabolisminKOA.

Inconclusion,EAisasafeandeffectivecomplementaryandalternativetherapyforKOA,whichcanalleviatepainandimprovejointfunction.ThetherapeuticeffectsofEAonKOAmaybeattributedtothemodulationoftheinflammatoryresponseandtheregulationofchondrocytemetabolismviavarioussignalingpathways.FurtherresearchisneededtooptimizetheEAprotocolandtoclarifythemechanismsofEAinthetreatmentofKOA.EAhasthepotentialtobewidelyappliedintheclinicaltreatmentofKOA,providingapromisingalternativetotraditionalpharmacologicalinterventionsInadditiontoitstherapeuticeffects,EAalsohasadvantagesoverconventionaltreatmentsforKOA,includingitsnon-invasivenature,minimalsideeffects,andpotentialforlong-lastingeffects.Unlikepharmacologicalinterventions,whichoftenhavesystemiceffectsandcancauseadversereactions,EAisalocalizedtreatmentthatdoesnotrequiremedication.Moreover,EAcanbeeasilyadjustedtoindividualpatients'needs,allowingforcustomizedandprecisetreatment.

AnotheradvantageofEAisitspotentialforlong-lastingeffects.WhiletraditionaltreatmentsforKOAmayprovidetemporaryrelief,thebenefitsoftenfadeovertimeandrequirerepeatedtreatments.Incontrast,severalstudieshavedemonstratedthatEAcanprovidesustainedpainreliefandfunctionalimprovementinpatientswithKOAforuptoseveralmonthsaftertreatment.ThismaybeattributedtothemodulatoryeffectsofEAontheunderlyingpathophysiologicalmechanismsofKOA,suchasinflammation,jointdegeneration,andneuropathicpain.

DespitethepromisingresultsofEAinthetreatmentofKOA,severalchallengesremain.OnemajorchallengeisthelackofstandardizedprotocolsforEAtreatment,includingtheoptimalneedleplacement,frequencyanddurationoftreatment,andstimulationintensity.Thevariabilityintheseparametersacrossdifferentstudiesmakesitdifficulttocompareandreplicatetheresults.Therefore,moreeffortsareneededtoestablishstandardizedprotocolsforEAtreatmentinKOA.

AnotherchallengeisthelimitedunderstandingofthemechanismsunderlyingthetherapeuticeffectsofEAinKOA.Whileseveralsignalingpathways,suchasthePI3K/AktandNF-κBpathways,havebeenimplicatedintheanti-inflammatoryandanti-degenerativeeffectsofEA,theexactmechanismsremainunclear.FurtherresearchisneededtoelucidatethecellularandmolecularmechanismsofEAinKOA,whichmayleadtothedevelopmentofnoveltherapeuticstrategiesforthiscommonanddebilitatingcondition.

Inconclusion,EAisasafeandeffectivetreatmentforKOA,providingpainreliefandimprovingjointfunction.ThetherapeuticeffectsofEAmaybeattributedtoitsmodulatoryeffectsontheinflammatoryresponseandchondrocytemetabolismviavarioussignalingpathways.AlthoughthereareseveralchallengesandlimitationsassociatedwithEAtreatmentforKOA,ithasthepotentialtobewidelyappliedintheclinicalsetting,providingapromisingalterna