脑缺血的病理生理3

■BiochemicalandMetabolicDerangementsinIschemicBrain

Thereareentirecascadesofchangesthatoccurinbraincellsdevoidofmetabolicsubstrate.Broadly,thesecanbeclassifiedintochangesincellsignalingandtransduction,inmetabolism,andingeneregulationandexpression.25Practically,ischemiaresultsindisruptionofcellularenergysubstrate,disruptionofionhomeostasis,andfailureofcellularstructuralintegrity.31

缺血性紊乱脑组织的生化和代谢

在没有代谢底物的脑细胞中存在着一系列的变化。大体上，这些可分为细胞信号转导和新陈代谢、基因调控和表达[25]。实际上，缺血导致细胞能量基质破坏，破坏离子平衡，和细胞结构完整性[31]。

Bymass,thebrainhasthehighestenergyrequirementsofanytissuewithinthebody.Thebrainreceives25%ofthecardiacoutputatrestandconsumes20%ofthebody’stotalenergystores.32TheprimaryfunctionofbloodflowtothebrainistodeliverglucoseandoxygenformitochondrialoxidativephosphorylationandproductionofATP.ATPisvitalasthemaincerebralenergytransfermolecule,whichisinvolvedinionhomeostasisandactionpotentialconductance(viatheNa+/K+–adenosinetriphosphatase[ATPase]),neurotransmitterreuptake,andsynthesisofcellularmoleculesandproteins.Theabsolutecellulareffectsofischemialargelydependontheavailablereservestoresofglucoseortheamountofglucoseandoxygensuppliedbycollateralcirculation.

与身体内的任何组织相比，大脑对能量的要求最高。大脑接收心脏的25%静止血输出，消耗人体总能量的20%[32]。大脑血流量的主要功能是提供线粒体葡萄糖和氧气氧化磷酸化，产生ATP。ATP作为大脑能量转移的主要分子，与离子平衡、动作电位传导（通过Na-K-ATP酶]），神经递质再摄取，和细胞分子、蛋白质的合成。缺血绝对的细胞影响很大程度上取决于现有侧支循环提供的葡萄糖或氧的量储备。

MaintenanceofrestingneuronalmembranepotentialsishighlydependentonsodiumandpotassiumexchangeviatheNa+/K+-ATPase,whichrequiresthehydrolysisofATP.Forsecondstominutesaftertheonsetofischemia,ATPlevelscanbekeptnearbaselinebycreatingmoreATPfromshort-termstoragemoleculessuchasphosphocreatine.33Astrocytesalsocontaintheirownsupplyofglycogen,andthiscanbeusedforATPsynthesisevenunderhypoxicconditionsviaanaerobicglycolysis.34Duringthisperiod,cellularprocessescontinueasnormalandtheyfurtherdepleteATPstores.AsATPlevelsfallandtheNa+/K+-ATPaseceasesitsfunction,themembranebe







































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