基于奧沙利鉑致周圍神經(jīng)病變模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響

基于奧沙利鉑致周圍神經(jīng)病變模型探討TheEffectsofHuangqiguizhiwuwuDecoctiononPlatinum-accumulationBasedontheModelofOxaliplatin-inducedPeripheralNeuropathyOxaliplatinNH2NH2PtOOOO5-Fluorouracil+Colorectalcancer1,2-Diaminocyclohexane（DACH）Oxalate基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響Cisplatin-resistantcancersPtPtNH2NH2Pt基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響AcuteO-IPNsyndromeDistalparesthesias,dysaesthesiasandmildmusclecontractionsofhands,feetandperioralregionHypersensitivitytocoldOccurinapproximately90%

ofpatientsRecoverwithinaweek基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響ChronicO-IPNsyndromePERSISTENTperipheralsensoryneuropathyoflimbs，involvinghypesthesiaand

difficultyinfinemovementlikewriting,buttoning,etcThemedianrecoveryisabout13-15weeksForatleast12monthsaftercessationofOXACumulativedoseofmorethan900mg/m2基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響Howtocureit?基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響O-IPNAntioxidantGlutathione(GSH)GlutamineCalcium-MagnesiumCalciumgluconate&magnesium

sulfateAnticonvulsantsCarbamazepine,OxcarbazepineGabapentin,PregabalinAntidepressantsDuloxetine,VenlafaxineMirtazapine,AmitriptylineNeurotrophic

factors(NTF)MecobalaminNervegrowthfactor(NGF)Ganglioside-monosialic(GM)CytidineDisodiumTriphosphate(CDT)基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響O-IPNneurologicsyndromesBloodarthralgia血痹BelongtoHuangqiguizhiwuwudecoction黃芪桂枝五物湯CureCure？？基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響TianJunandcollaboratorsuseMeta-analysistoinvestigatethelinksbetween‘Bloodarthralgia’theoryofChinesetraditionalmedicineandO-IPN,andtheeffectivenessandseverityofHuangqiguizhiwuwudecoctionontheeffectforthetreatmentofO-IPN,basedontheoutcomesof368patients,6clinicaltrials.TianJ,YaoXQ,WuXY,etal.SystematicReviewandMetaAnalysisonEfficacyofHuangqiGuizhiWuwuDecoctionforOxaliplatin-inducedPeripheralNeurotoxicity[J].ChineseJournalofExperimentalTraditionalMedicalFormulae,2014,19(22):325-330.Huangqiguizhiwuwudecoction(1)CanpreventandcureO-IPN(2)Canreducetheincidenceofsevereperipheralneurotoxicity(3)Canalleviatetheinhibitionofsensorynerveconductionvelocity(SNCV)ofO-IPN(4)Hasacertaindegreeofsecurityforclinicalapplication基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響Whatisthemechanism?基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響ChronicO-IPNMitochondrialdysfuction

ImbalanceintheintracellularredoxpotentialElevationof

reactiveoxygenspecies(ROS)FormDNAadductsinmitochondria

FormDNAadductsinnuclearPtaccumulatesinDRGRedundantmitochondrialdamageNeuronapoptosisNeurogenicin?ammationNeurodegenerationFormationdecreasingofNGFDemyelinationMicrotubulesdamageMAPKsPARPP53TRPsBax↑Bcl-2↓P38ERKImpairmentinaxonaltransmissionSOD↓Ca2+PeripheralnociceptorsensitizationMDA↑基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響ChronicO-IPNMitochondrialdysfuction

ImbalanceintheintracellularredoxpotentialElevationof

reactiveoxygenspecies(ROS)FormDNAadductsinmitochondria

FormDNAadductsinnuclearPtaccumulatesinDRGRedundantmitochondrialdamageNeuronapoptosisNeurogenicin?ammationNeurodegenerationFormationdecreasingofNGFDemyelinationMicrotubulesdamageMAPKsPARPP53TRPsBax↑Bcl-2↓P38ERKImpairmentinaxonaltransmissionSOD↓Ca2+PeripheralnociceptorsensitizationMDA↑空白組1000×中藥組1000×模型組1000×基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響Directlyanti-oxidizethroughreactingwithROSIndirectlyanti-oxidizethroughpreventingthedecreaseorinactivationofantioxidant,likeSOD,GSH-Px,andsoonIndirectlyanti-oxidizethroughreducingtheexpressionofTRPsmRNA,whichbringCa2+

totakepartinoxidativestressInhibitionofMAPKs,includingP38andERK1/2InhibitionofP53signaltransductionpathwayPreviousstudiesshowedHuangqiguizhiwuwudecoctioncancurechronicO-IPNbythefollowingmechanisms:基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響EffectsofthecompositionofHuangqiguizhiwuwudecoctionMilkvetchRoot(黃芪)AstragalosideIV(黃芪甲苷),withthebestbiologicalactivityamongthecompositionsofMilkvetchRoot,hasalotofeffectsincludingantioxidant,improvingimmunedefense,promotingbloodcirculation,strengthenimmunityandsoon基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響EffectsofthecompositionofHuangqiguizhiwuwudecoctionMilkvetchRoot(黃芪)AstragalusPolysacharin(黃芪多糖,APS),Totalflavonoidsofastragalus(黃芪總黃酮,TFA)aredemonstratedwithantioxidanteffectγ-amiinnobutyricacid(伽馬氨基丁酸,GABA)hastheabilityofvasculardilation基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響EffectsofthecompositionofHuangqiguizhiwuwudecoctionPeonyRoot(白芍)Totalglucosidesofpaeony(芍藥總苷,TGP),dominantsectorofPeonyRoot,haveeffectsincludingantioxidant,vasculardilation,strengthenimmunity,anticonvulsion,anti-inflammation,analgesiaandsoonPentagalloylglucose(五沒食子?；咸烟?PGG)hastheabilityofvasculardilation基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響EffectsofthecompositionofHuangqiguizhiwuwudecoctionCassia

Twig

(桂枝)Cinnamaldehyde(桂皮醛,TGP),acompositionofCassiaTwig,haseffectsincludingvasculardilation,anti-inflammation,analgesiaandsoonCinnamicacid(桂皮酸)hastheabilityofvasculardilation基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響EffectsofthecompositionofHuangqiguizhiwuwudecoction(1)VasculardilationAstragalosideIV(黃芪甲苷),γ-amiinnobutyricacid(伽馬氨基丁酸GABA),Totalglucosidesofpaeony(芍藥總苷,TGP),Cinnamaldehyde(桂皮醛,TGP),Cinnamicacid(桂皮酸)(2)StrengthenimmunityAstragalosideIV(黃芪甲苷),AstragalusPolysacharin(黃芪多糖,APS),Totalglucosidesofpaeony(芍藥總苷,TGP)基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響ChronicO-IPNMitochondrialdysfuction

ImbalanceintheintracellularredoxpotentialElevationof

reactiveoxygenspecies(ROS)FormDNAadductsinmitochondria

FormDNAadductsinnuclearRedundantmitochondrialdamageNeuronapoptosisNeurogenicin?ammationNeurodegenerationFormationdecreasingofNGFDemyelinationMicrotubulesdamageMAPKsPARPP53TRPsBax↑Bcl-2↓P38ERKImpairmentinaxonaltransmissionSOD↓Ca2+PeripheralnociceptorsensitizationMDA↑PtaccumulatesinDRGHuangqiguizhiwuwudecoctioncouldcurechronicO-IPNbyreducingplatinum-accumulationintheDRG基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響HuangqiguizhiwuwudecoctioncouldcurechronicO-IPNbyreducingplatinum-accumulationintheDRGClinicalsymptomDrugcompositionPreviousexperiments基于O-IPN模型探討黃芪桂枝五物湯對(duì)鉑蓄積的影響HuangqiguizhiwuwudecoctioncouldcurechronicO-IPNby