OxAc对大鼠缺血性脑损伤的保护作用研究

目的:观察静脉注射草酰乙酸(oxaloacetate,OxAc)对大鼠局灶性脑缺血的神经保护作用.方法:线拴法建立大鼠大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)再灌注损伤模型,54只雄性SD大鼠随机分为5组:Sham组(n=6),MCAO+0.9%NS组(n=12),MCAO+OxAc组(n=12),MCAO+OxAc+GOT组(n=12)和MCAO+OxAc+Maleate组(n=12).脑缺血2h于再灌注即刻给予不同药物静脉注射,分别检测各组大鼠血清与脑脊液中谷氨酸(glutamate,Glu)体积质量分数、神经行为学评分、脑梗死体积及神经元脱失情况.结果:脑缺血2h后大鼠脑脊液中的Glu体积质量分数显著上升(p<0.001),血浆中Glu体积质量分数无明显变化.静脉注射OxAc可以迅速而明显地降低脑缺血大鼠血浆和脑脊液中的Glu体积质量分数(p<0.05);与MCAO+0.9%NS组相比,OxAc的应用可以明显提高大鼠神经行为学评分(p<0.05)、减小脑梗死体积(p<0.01)、明显改善术后大鼠相关脑区神经元脱失现象;同时静脉注射谷草转氨酶(Glutamate-oxaloacetate transaminase,GOT)可以促进OxAc的作用,而同时应用GOT特异性抑制剂马来酸盐(Maleate)可以减弱OxAc的上述作用效果.结论:静脉注射OxAc对大鼠急性局灶性脑缺血具有明显的神经保护作用,且此作用主要是通过其作为血液中的"谷氨酸清道夫"而实现的.

ProtectiveEffectofOxAconLocalCerebralIschemiaInjuryinRat

Objective:ToobservetheneuroprotectiveeffectofOxAconlocalcerebralischemiainrats. Methods:Thelocalcerebralischemia/reperfusionmodelwasestablishedbyintraluminalthreadocclusion ofthemiddlecerebralarteryocclusion(MCAO)inrats.Fifty-fourmaleSDratswererandomlydividedintofivegroups: Shamgroup(n=6),MCAO+0.9%NSgroup(n=12),MCAO+OxAcgroup(n=12), MCAO+OxAc+GOTgroup(n=12)andMCAO+OxAc+Maleategroup(n=12).Twohoursaftercerebralischemia, variousdrugsweregiven,thenglutamateconcentrationinserum,Longascores,cerebral infarctionvolumeandneuronaldeathmeasurementwereusedtoassessthechangesofischemicbraintissuesindifferentgroups. Results:TwohoursafterMCAO,thecerebrospinalfluidglutamatelevelsinrats increasedremarkably(p<0.001),buttheplasmaglutamatelevelsinratsdidnotchangestatistically.Ox- Acdecreasedthecerebrospinalfluidandplasmaglutamatelevelsincerebralischemisratsrapidlyandobviously( p<0.05).ComparedwiththeMCAO+0.9%NSgroup,OxAcintravenousinjectionincreasedthe Longascores(p<0.05)anddecreasedtheinfarctionvolume(p<0.01)andneuronaldeathnumber.Glutamate- oxaloacetatetransminase(GOT)enhancedtheeffectofOxAc,butthespecificinhibitorofGOT, maleate,attenuatedtheeffectofOxAc.Conclusion:OxAchasamarkedneuroprotectiveeffectonlocal cerebralischemiainrats,andthiseffectisrelatedprimarilytoitsbloodglutamatescavengingactivity.