神經(jīng)保護(hù)與血液稀釋

Posner,KL.APSFNewsletter,2001:37.美國(guó)麻醉學(xué)會(huì)統(tǒng)計(jì)的起訴并發(fā)癥情況*p=0.05vs1970;+p=0.05vs1980圍術(shù)期神經(jīng)損傷2-6%心臟手術(shù)病人

JThorcCardiovascSurg1992;104:1510-72.1%頸動(dòng)脈內(nèi)膜剝脫術(shù)病人

NEnglJMed1991;325:445-535-10%胸腹主動(dòng)脈瘤手術(shù)合并截癱

AnnSurg2002;236:471-9圍術(shù)期腦中風(fēng)

死亡率Stephen 1984

33%Parikh 1993

26%Landercasper 1990*

60%*

AllpatientswithpreviousCVAProtectiveStrategyAnesthetics

inhalationalintravenousOxygenfreeradicalscavengersPreconditioning-inducedtoleranceChinesetraditionalherbsHemodilutionNeuroprotectionbyHemodilutionLowmolecularweightdextranAlbuminGelatinAlpha-alphadiaspirincross-linkedhemoglobinHydroxyethylstarch

Effectsofacutenormovolemichemodilutioninprotectingbrainafterischemia.JChinClinRehab.2004;8(7):1353-5

MCAOratmodelAcuteNormovolemicHemodilution

Hct

47.3±3.3%→30.7±3.6%Hb152.1±10.4→99.5±11.9g/LbraininfarctsizeMeiHX,etal.JChinClinRehab.2004;8(7):1353-6AnimalModel

MCAORatNeurologicDeficitScoresInfarctVolumeByTTCStain

InfarctVolumeRatBrainIcedsaline10minCoronalsections(2mm)

2％TTC10％Formalin37℃30minPhotograph,analysis24hHemodynamicsandhematologyparametersNeurologicdeficitscores(NDS)assessedat24hoursafterreperfusionbraininfarctsizeAnimalModelSpinalCordIschemiaRabbitHind-limbMotorFunctionScoring

NumberofNormalMotorNeuronsHindlimbmotorfunctionTarlovscoresMedian(range)P12345678CON010010220.5（0-1）NS114311332（1-4）0.029V321342433（1-4）0.008Thenumberofnormalmotorneurons

▲△Normalmotorneuronnumbers01020304050CONNSVoluven●●●▲●●●●●▲▲▲▲▲▲△△△△△△***TheEffectofHemodilutiononCerebralBloodFlowVelocity

inAnesthetizedPatientsBruderN,etal.TheEffectofHemodilutiononCerebralBloodFlowVelocityinAnesthetizedPatients.AnesthAnalg,1998;86:320-4

TheBestHctLevel?DuringDeepHypothermicBypass

EffectsofHematocritonCerebralMicrocirculationandTissueOxygenation.

DuebenerLF,etal.

Circulation2001;104DuebenerLF,etal.Circulation2001;104DuringDeepHypothermicBypass

EffectsofHematocritonCerebralMicrocirculationandTissueOxygenation.Circulation2001;104

ThestudyshowsthesuperiorityofahigherHct(30%)relativetolowerHctvaluesforcerebraltissueoxygenationduringcardiacoperations,includingdeephypothermicbypassandcirculatoryarrest.HemodynamicsandhematologyNeurologicdeficitscores(NDS)fromassessed24hoursafterreperfusionBraininfarctsize20AComparisonofCompleteBloodReplacementWithVaryingHematocritLevelsonNeurologicalRecoveryinaPorcineModelofProfoundHypothermic(<5°C)CirculatoryArrest

SekaranP,etal.

AnesthAnalg,2001;92:329-3427-31kgpigsHct0%,5%,15%(6%Hetastarch)60mincardiacarrestunder<5℃EvaluationofneurologicalrecoverySekaranP,etal.AnesthAnalg2001;92:329-34ProblemsHemodilutionitselfcannotprovideenoughneuroptrotectionNeedtofindoutmoreprotectantsNon-ischemicpreconditioningsPossibleClinicalApplicationsIschemictoleranceasamodeltostudyendogenousneuro-protectivemechanisms.IschemiacausedbyMCAOinducesendogenousneuroprotection.ITdoesn’taffectthedestructivemechanismsofischemia.---fromDirnaglU,etal.Trendsinneuroscience2003;26(5)缺血預(yù)處理

一個(gè)好研究模型（機(jī)制）可用于心臟手術(shù)的保護(hù)不能直接用于腦保護(hù)非缺血預(yù)處理措施尋找我們致力于研究高壓氧預(yù)處理異氟醚預(yù)處理電針刺激預(yù)處理動(dòng)物模型大腦中動(dòng)脈栓塞(MCAO)大鼠腦缺血模型

神經(jīng)功能障礙評(píng)分（NDS）腦梗死容積測(cè)定（TTC）腎下主動(dòng)脈(IRA)阻斷大白兔脊髓缺血模型

后肢運(yùn)動(dòng)功能評(píng)分（Tarlov）病理學(xué)觀察（脊髓前角運(yùn)動(dòng)神經(jīng)元計(jì)數(shù)）高壓氧氧自由基腦和脊髓缺血耐受？預(yù)處理思路高壓氧預(yù)處理?xiàng)l件2.5ATA100%O21h/d3d/5dDongHL,XiongL,etal.Anesthesiology,2002;96:907-12DongHL,XiongLetal.Anesthesiology,2002;96:907-12問題缺血耐受高氧部分？高壓+高氧？高壓部分？高壓氧DongHL,XiongL,etal.Anesthesiology,2002;96:907-12DongHL,XiongL,etal.Anesthesiology,2002;96:907-12HBO預(yù)處理效應(yīng)取決于腦損傷的程度

ChinMedJ,2000;113(9):836-839永久性缺血暫時(shí)性缺血證實(shí)HBO直接誘導(dǎo)脊髓神經(jīng)元產(chǎn)生缺血耐受LifeScience,2007;80(12):1087-93脊髓原代神經(jīng)元培養(yǎng)（β-tubulin免疫熒光）脊髓神經(jīng)元單細(xì)胞凝膠電泳ControlH2O2H2O2+HBOSODCATDMTU大白兔HBO處理SP缺血缺血耐受24h5dSOD,CAT↑氧自由基Nie,etal.JCerebBloodFlowMetab2006;26:666-74證實(shí)JAK-STAT通路參與腦缺血再灌注損傷，表現(xiàn)為腦缺血再灌注后星形膠質(zhì)細(xì)胞和神經(jīng)元中pSTAT3顯著增加pSTAT3NeuNMergeGFAPMergepSTAT3GFAP:星形膠質(zhì)細(xì)胞NeuN:神經(jīng)元細(xì)胞

1:假手術(shù)組

2:缺血2h再灌注30min3:缺血2h再灌注2h4:缺血2h再灌注24hCTX:大腦皮層；HIPP:海馬CTXHIPPWesternBlot免疫熒光發(fā)現(xiàn)STAT3抑制劑AG490顯著減輕腦損傷TTC染色腦梗死容積神經(jīng)行為學(xué)評(píng)分首次在體內(nèi)證實(shí)DMTU呈劑量依賴性地減少pSTAT3

證實(shí)氧自由基與STAT3活化有關(guān)DMTU對(duì)pSTAT3影響（CTX）110.80.60.40.20OD:pSTAT3/STAT3ConDMTU1DMTU2DMTU3

DMTU對(duì)pSTAT3影響（HIPP）10.80.60.40.20OD:pSTAT3/STAT3ConDMTU1DMTU2DMTU3WesternBlot

1:I/Rgroup2:DMTU13:DMTU24:DMTU3

發(fā)現(xiàn)HBO預(yù)處理使腦缺血再灌注后STAT3活化減少說(shuō)明HBO可能通過抑制STAT3活化發(fā)揮腦保護(hù)效應(yīng)CTXHIPPpSTAT3STAT3actin1234561234561,3,5:缺血再灌注；2,4,6:HBO預(yù)處理后缺血再灌注

1,2:缺血2h再灌注30min；3,4:缺血2h再灌注2h；5,6:缺血2h再灌注24h

WesternBlotHBO預(yù)處理誘導(dǎo)缺血耐受的初步機(jī)制JCerebBloodFlowMetab,2006;26:666-674氧自由基大量生成缺血再灌注損傷pSTAT3↑缺血再灌注HBO預(yù)處理氧自由基抗氧化酶系統(tǒng)活性↑清除氧自由基pSTAT3↓缺血耐受臨床遇到的問題頸椎術(shù)后缺血再灌注損傷、水腫HBO預(yù)處理對(duì)這類病人有效嗎？與骨科合作觀察90例頸椎手術(shù)病人

FanSD,etal.TheclinicalefficacyofHBOpreconditioningHBO預(yù)處理對(duì)頸椎手術(shù)的效果HBO預(yù)處理能有效地減輕術(shù)后脊髓再灌注損傷及反跳性水腫術(shù)后1月和1年的隨訪觀察，HBO預(yù)處理有助于脊髓功能的恢復(fù)成功的第一步問題：HBO并非普及更簡(jiǎn)便方法：吸氧？自由基缺血耐受形成高壓氧預(yù)處理長(zhǎng)時(shí)高濃度吸氧？結(jié)果

ADZhangXJ,etal.CanJAnesth,2004;51(3)ZhangXJ,etal.CanJAnesth,2004;51(3)自由基的作用異氟醚?最常用的吸入麻醉藥！西京醫(yī)院10,000例/年如有預(yù)處理效應(yīng)……!XiongL,etal.AnesthAnalg2003;96:233-7XiongL,etal.AnesthAnalg2003;96:233-7

O21hMCAO2hreperfusion24hO2ControlDPCPXIsoDPCPX＋I(xiàn)soDMSO＋I(xiàn)soIsoIsoIso1h1h1h1hMCAO2hMCAO2hMCAO2hMCAO2hReperfusion24hreperfusion24hreperfusion24hreperfusion24h

15min1h1h2h24h(time)TheroleofadenosineA1receptorTheinfarctsizeat24hoursafterreperfusion(n=10each)(*P<0.01vsControl,DPCPXandDPCPX+Isogroups)*TheroleofadenosineA1receptor*LiuYH,etal.CanadianJAnesth2006;53(2)EffectoflidocaineonITinducedbyisoflurane(n=10each)*P<0.01vsControl,＃P<0.05vsLidocaineandLidocaine+IsoLiuYH,etal.CanadianJAnesth2006;53(2)*＃電針預(yù)處理?鮮明的中國(guó)特色使用方便、安全價(jià)格便宜、宜于推廣電針刺激：15HZ,1mA050200*

100150250300350ControlISOEAEffectofacupuncturepreconditioningoninfarctsizeinducedbyMCAO(*P<0.05vscontrol)InfarctVolume(mm3)XiongL,etal.ChinMedJ20033;116:108-1110100200300ControlPBELEBInfarctVolume(mm3)*

Effectofspecificityofacupoint(*P<0.05)AcupunturePreconditioningLuZH,etal.JChinAcupunture2002百會(huì)穴(DU20)

百會(huì)穴旁1cm穴位特異性p<0.01vsControl,PBp<0.05vsEA2p<0.05vsControl,PBIinfarctsize(mm3)不同穴位的效果百會(huì)(DU20)風(fēng)池(GB20)足三里(ST36)電針刺激最佳條件的確定結(jié)果三種電流間無(wú)統(tǒng)計(jì)差別(P=0.37)波形間有顯著的差別