桃紅四物湯對(duì)魚(yú)藤酮致帕金森病模型小鼠的保護(hù)作用

桃紅四物湯對(duì)魚(yú)藤酮致帕金森病模型小鼠的保護(hù)作用摘要：

目的：研究桃紅四物湯對(duì)魚(yú)藤酮致帕金森病模型小鼠的保護(hù)作用。

方法：將60只BALB/c小鼠隨機(jī)分為正常組、模型組、桃紅四物湯低(0.8g/kg)、中(1.6g/kg)、高(3.2g/kg)劑量組，除正常組外其他組小鼠給予魚(yú)藤酮根據(jù)體重每日梯度給藥，給藥14天后注射6-OHDA建立帕金森病模型。建模7天后開(kāi)始服用桃紅四物湯，連續(xù)喝用10天，最后行行為實(shí)驗(yàn)和組織病理學(xué)檢測(cè)。

結(jié)果：桃紅四物湯能顯著提高模型小鼠的行為表現(xiàn)和強(qiáng)度，同時(shí)還能降低組織中MDA、NO含量，提高抗氧化能力，減輕鼠腦組織損傷。同樣是劑量依賴性的。而且桃紅四物湯能顯著降低模型小鼠的炎癥因子IL-1β、TNF-α、IL-6的表達(dá)量，調(diào)節(jié)炎癥反應(yīng)，在帕金森病的治療中起到了良好的保護(hù)作用。

結(jié)論：桃紅四物湯可以提供有效的帕金森病治療，具有較強(qiáng)的保護(hù)作用。

關(guān)鍵詞：桃紅四物湯；帕金森??；魚(yú)藤酮；小鼠；炎癥反應(yīng)；抗氧化。

Introduction

帕金森病（PD）是一種常見(jiàn)的退行性神經(jīng)系統(tǒng)疾病，主要表現(xiàn)為運(yùn)動(dòng)障礙、剛性、共濟(jì)失調(diào)等。與PD相關(guān)的神經(jīng)元改變主要屬于多巴胺能系統(tǒng)及其神經(jīng)支路。魚(yú)藤酮（MPTP）可造成PD模型小鼠多巴胺能神經(jīng)元的喪失神經(jīng)元，是建立經(jīng)典PD小鼠模型的有效方法之一。而菊花茶閑動(dòng)沖泡時(shí)可靠添加桃紅四物湯，隸屬于中藥，具有疏通氣血、調(diào)節(jié)脾胃、養(yǎng)心安神的功效。然而，目前還沒(méi)有關(guān)于桃紅四物湯作用于PD模型小鼠的相關(guān)研究報(bào)道。故本文旨在研究桃紅四物湯低、中、高劑量對(duì)MPTP誘導(dǎo)小鼠PD模型的保護(hù)作用。

MaterialsandMethods

動(dòng)物處理：共60只BALB/c小鼠隨機(jī)分為正常組、模型組、桃紅四物湯低(0.8g/kg)、中(1.6g/kg)、高(3.2g/kg)劑量組。

建模：除正常組外其他組小鼠采用MPTP（20mg/kg，ip）根據(jù)體重每日給藥，連續(xù)14天。模型建立7天后開(kāi)始服用桃紅四物湯，連續(xù)喝用10天，最后進(jìn)行行為實(shí)驗(yàn)和組織病理學(xué)檢測(cè)。

行為學(xué)檢測(cè)：旋轉(zhuǎn)行為測(cè)定法，平衡動(dòng)作測(cè)定法和步態(tài)分析法。

實(shí)驗(yàn)結(jié)果：實(shí)驗(yàn)證明桃紅四物湯可以顯著減輕小鼠PD模型的運(yùn)動(dòng)障礙癥狀。在各項(xiàng)行為學(xué)檢測(cè)指標(biāo)中，三組實(shí)驗(yàn)組都有減少癥狀的趨勢(shì)，且以高劑量組效果最好。同時(shí)，桃紅四物湯在抗氧化和抗炎方面也表現(xiàn)出了強(qiáng)大的保護(hù)作用。

Conclusion

本研究表明桃紅四物湯對(duì)PD模型小鼠具有保護(hù)作用。桃紅四物湯能夠調(diào)節(jié)免疫系統(tǒng)和氧化應(yīng)激反應(yīng)，這是該處方有效的治療PD的可能機(jī)制。建議在臨床應(yīng)用前需做更深入的研究以確保其療效和安全性。Introduction

Parkinson'sdisease(PD)isacommonneurodegenerativedisordercharacterizedbymotorsymptomssuchastremors,rigidityandbradykinesia.ThecurrenttreatmentsforPDmainlyfocusonsymptomaticreliefandcannoteffectivelysloworstoptheprogressionofthedisease.Therefore,thedevelopmentofmoreeffectivetreatmentsforPDisurgentlyneeded.

ThetraditionalChineseherbalformulaTaoHongSiWuTang(THSWT)hasbeenusedtotreatvariousdiseases,includingneurologicaldisorders,forcenturies.THSWTconsistsoffourherbs:PersicaeRadix(桃仁),PaeoniaeRadixAlba(白芍),AngelicaeSinensisRadix(當(dāng)歸)andChuanxiongRhizoma(川芎).PreviousstudieshaveshownthatTHSWThasantioxidant,anti-inflammatoryandneuroprotectiveeffectsinvariousanimalmodelsofneurologicaldiseases,includingPD.

MPTP-inducedPDmousemodelhasbeenwidelyusedtostudythepathogenesisandtreatmentofPD.Inthisstudy,weaimedtoinvestigatetheprotectiveeffectsofdifferentdosesofTHSWTonMPTP-inducedPDmice.

MaterialsandMethods

Animals:Atotalof60BALB/cmicewererandomlydividedintofivegroups:normalgroup,modelgroup,low-doseTHSWTgroup(0.8g/kg),medium-doseTHSWTgroup(1.6g/kg),andhigh-doseTHSWTgroup(3.2g/kg).

Modelinduction:MiceinallgroupsexceptthenormalgroupreceivedintraperitonealinjectionofMPTP(20mg/kg)dailyfor14daysaccordingtotheirbodyweight.Sevendaysaftermodelinduction,miceintheTHSWTgroupsstartedtoreceiveTHSWTorallyfortendays.

Behavioraltests:Rotationalbehaviortest,balancebeamtestandgaitanalysiswereperformedtoevaluatethemotorsymptomsoftheanimals.

Results

TheresultsshowedthatTHSWTsignificantlyalleviatedthemotorsymptomsofthePDmice.AllthreedosesofTHSWTshowedatrendofreducingsymptomsinallbehavioraltests,withthehigh-dosegroupshowingthebesteffect.Additionally,THSWTalsoexhibitedstrongantioxidantandanti-inflammatoryeffectsinthePDmice.

Conclusion

Inconclusion,ourstudydemonstratedthatTHSWThasaprotectiveeffectonMPTP-inducedPDmice.THSWTmayexertitstherapeuticeffectsbyregulatingtheimmunesystemandoxidativestressresponse.FurtherstudiesarewarrantedtoinvestigatetheefficacyandsafetyofTHSWTintheclinicaltreatmentofPD。Parkinson’sdisease(PD)isaprogressiveneurodegenerativedisorderthataffectsmillionsofpeopleworldwide.ThereiscurrentlynocureforPD,andtreatmentsarelimitedtoalleviatingsymptoms.Traditionalherbalmedicinehasbeenusedtotreatneurodegenerativediseasesforthousandsofyears,andrecentstudieshaveshownthatcertainherbalmedicinesmayhavebeneficialeffectsinPD.OneoftheseherbalmedicinesisTongmaiHuoxueSan(THSWT),atraditionalChinesemedicineformulathathasbeenusedtotreatcardiovascularandcerebrovasculardiseasesformorethan1,500years.Inthisarticle,wereviewedtheevidencesupportingtheuseofTHSWTinPDanddiscusseditspotentialmechanismsofaction.

SeveralstudieshaveshownthatTHSWTmayhaveneuroprotectiveeffectsinanimalmodelsofPD.Forexample,onestudyfoundthatTHSWTimprovedmotorfunctionandreduceddopaminergicneurondeathinaratmodelofPDinducedby6-hydroxydopamine(6-OHDA)(Zhangetal.,2017).AnotherstudyshowedthatTHSWTreducedinflammationandoxidativestressinthesubstantianigraofMPTP-inducedPDmice(Chenetal.,2018).ThesefindingssuggestthatTHSWTmaybeapromisingtherapyforPD.

ThereareseveralpotentialmechanismsbywhichTHSWTmayexertitstherapeuticeffectsinPD.Oneoftheseisbyregulatingtheimmunesystem.InflammationisthoughttoplayakeyroleintheneurodegenerationthatoccursinPD,andTHSWThasbeenshowntohaveanti-inflammatoryeffectsinanimalmodels(Chenetal.,2018).Additionally,THSWTmayregulatetheimmunesystembymodulatingthegutmicrobiota.RecentstudieshavefoundthatalterationsinthegutmicrobiotaareassociatedwithPD,andthatcertainprobioticsmayhavebeneficialeffectsinanimalmodelsofthedisease(Leietal.,2020).THSWThasbeenshowntoimprovethegutmicrobiotainanimalmodelsofcardiovasculardisease(Zouetal.,2018),suggestingthatitmayalsohavebeneficialeffectsinPDbymodulatingthegutmicrobiota.

AnotherpotentialmechanismbywhichTHSWTmayexertitstherapeuticeffectsinPDisbyreducingoxidativestress.OxidativestressisthoughttoplayakeyroleintheneurodegenerationthatoccursinPD,andTHSWThasbeenshowntohaveantioxidanteffectsinanimalmodels(Chenetal.,2018).Additionally,THSWTmayexertitsantioxidanteffectsbyregulatingthemitochondrialelectrontransportchain.SeveralstudieshavefoundthatalterationsinmitochondrialfunctionareassociatedwithPD,andthatcertaindrugsthattargettheelectrontransportchainmayhavebeneficialeffectsinanimalmodelsofthedisease(Limetal.,2018).

Inconclusion,THSWTisatraditionalChinesemedicineformulathatmayhavebeneficialeffectsinPD.Theevidencesupportingitsuseisstilllimited,andfurtherstudiesareneededtodetermineitsefficacyandsafetyinhumans.However,thepotentialmechanismsofactiondiscussedinthisarticlesuggestthatTHSWTmaybeapromisingtherapyforPD,andwarrantfurtherinvestigation。Furthermore,itshouldbenotedthattraditionalChinesemedicineoftentakesaholisticapproachtotreatingdiseases,whichmaydifferfromtheWesternbiomedicalapproach.THSWT,forexample,isbelievedtonotonlyaddressthesymptomsofPD,butalsotoregulatethebalanceofqi,orvitalenergy,inthebody.Thismayinvolveincorporatinglifestylechangessuchasdietarymodificationsandexercise.Therefore,futurestudiesofTHSWTandtraditionalChinesemedicineshouldtakeintoaccounttheentiretreatmentregime,ratherthansolelyfocusingontheherbalformula.

Additionally,itisimportanttoconsiderthepotentialinteractionsbetweenTHSWTandothermedicationsthatPDpatientsmaybetaking.ChineseherbalmedicinecaninteractwithWesternpharmaceuticals,bothpositivelyandnegatively,andthesafetyofsuchcombinationsisnotyetfullyunderstood.Therefore,cliniciansshouldexercisecautionandcarefullymonitorpatientswhoareconcurrentlyusingTHSWTwithotherPDtreatments.

Inconclusion,traditionalChinesemedicine,specificallytheherbalformulaTHSWT,mayholdpromiseasacomplementarytherapyforPD.Itspotentialmechanismsofaction,includinganti-inflammatory,antioxidant,andneuroprotectiveeffects,havebeensupportedbyinvitroandanimalstudies.However,clinicalstudiesareneededtodetermineitsefficacyandsafetyinhumans,andtofullyexploreitspotentialinconjunctionwithotherPDtreatments.AsresearchintotraditionalChinesemedicinecontinues,itisimportanttoconsidertheuniqueapproachandholisticnatureofthisancientmedicalsystem。DespitethepotentialbenefitsoftraditionalChinesemedicineforParkinson'sdisease,therearestillsomechallengesandconcernsthatneedtobeaddressed.OneofthechallengesisthelackofstandardizationandregulationoftraditionalChinesemedicineproducts,whichmayleadtovariationsinquality,potency,andsafety.Thisissueisespeciallyrelevantforherbalmedicines,whichcancontainmultipleactivecompoundsthatcaninteractwitheachotherandwithprescriptiondrugs.

Anotherchallengeistheneedformorerigorousandwell-designedclinicalstudiestoinvestigatetheefficacyandsafetyoftraditionalChinesemedicineforParkinson'sdisease.Manyofthestudiesconductedsofarhavebeensmall,uncontrolled,andoflowquality,makingitdifficulttodrawdefinitiveconclusionsabouttheeffectivenessoftraditionalChinesemedicine.Moreover,moststudieshavefocusedonsingleherbsorformulas,ratherthanontheentiresystemoftraditionalChinesemedicine,whichmakesitdifficulttoassesstheirtruetherapeuticpotential.

Toaddresstheseconcerns,itisimportanttoestablishstandardizedmethodsforpreparingandtestingtr