桃红四物汤对鱼藤酮致帕金森病模型小鼠的保护作用

桃红四物汤对鱼藤酮致帕金森病模型小鼠的保护作用摘要：

目的：研究桃红四物汤对鱼藤酮致帕金森病模型小鼠的保护作用。

方法：将60只BALB/c小鼠随机分为正常组、模型组、桃红四物汤低(0.8g/kg)、中(1.6g/kg)、高(3.2g/kg)剂量组，除正常组外其他组小鼠给予鱼藤酮根据体重每日梯度给药，给药14天后注射6-OHDA建立帕金森病模型。建模7天后开始服用桃红四物汤，连续喝用10天，最后行行为实验和组织病理学检测。

结果：桃红四物汤能显著提高模型小鼠的行为表现和强度，同时还能降低组织中MDA、NO含量，提高抗氧化能力，减轻鼠脑组织损伤。同样是剂量依赖性的。而且桃红四物汤能显著降低模型小鼠的炎症因子IL-1β、TNF-α、IL-6的表达量，调节炎症反应，在帕金森病的治疗中起到了良好的保护作用。

结论：桃红四物汤可以提供有效的帕金森病治疗，具有较强的保护作用。

关键词：桃红四物汤；帕金森病；鱼藤酮；小鼠；炎症反应；抗氧化。

Introduction

帕金森病（PD）是一种常见的退行性神经系统疾病，主要表现为运动障碍、刚性、共济失调等。与PD相关的神经元改变主要属于多巴胺能系统及其神经支路。鱼藤酮（MPTP）可造成PD模型小鼠多巴胺能神经元的丧失神经元，是建立经典PD小鼠模型的有效方法之一。而菊花茶闲动冲泡时可靠添加桃红四物汤，隶属于中药，具有疏通气血、调节脾胃、养心安神的功效。然而，目前还没有关于桃红四物汤作用于PD模型小鼠的相关研究报道。故本文旨在研究桃红四物汤低、中、高剂量对MPTP诱导小鼠PD模型的保护作用。

MaterialsandMethods

动物处理：共60只BALB/c小鼠随机分为正常组、模型组、桃红四物汤低(0.8g/kg)、中(1.6g/kg)、高(3.2g/kg)剂量组。

建模：除正常组外其他组小鼠采用MPTP（20mg/kg，ip）根据体重每日给药，连续14天。模型建立7天后开始服用桃红四物汤，连续喝用10天，最后进行行为实验和组织病理学检测。

行为学检测：旋转行为测定法，平衡动作测定法和步态分析法。

实验结果：实验证明桃红四物汤可以显著减轻小鼠PD模型的运动障碍症状。在各项行为学检测指标中，三组实验组都有减少症状的趋势，且以高剂量组效果最好。同时，桃红四物汤在抗氧化和抗炎方面也表现出了强大的保护作用。

Conclusion

本研究表明桃红四物汤对PD模型小鼠具有保护作用。桃红四物汤能够调节免疫系统和氧化应激反应，这是该处方有效的治疗PD的可能机制。建议在临床应用前需做更深入的研究以确保其疗效和安全性。Introduction

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

ThetraditionalChineseherbalformulaTaoHongSiWuTang(THSWT)hasbeenusedtotreatvariousdiseases,includingneurologicaldisorders,forcenturies.THSWTconsistsoffourherbs:PersicaeRadix(桃仁),PaeoniaeRadixAlba(白芍),AngelicaeSinensisRadix(当归)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