OxAc对大鼠缺血性脑损伤的保护作用研究  

Protective Effect of OxAc on Local Cerebral Ischemia Injury in Rats

作　　者：付利娟[1] 温纯洁[2] 丁裕斌[3] 吴兰香[2] 

机构地区：[1]重庆医科大学中医药学院,重庆400016 [2]重庆医科大学生命科学研究院,重庆400016 [3]重庆医科大学公共卫生学院,重庆400016

出　　处：《西南大学学报（自然科学版）》2012年第8期48-52,共5页Journal of Southwest University(Natural Science Edition)

基　　金：国家自然科学基金资助项目(84402511);重庆市教育委员会科学技术研究基金资助项目(KJ090306);重庆市自然科学基金资助项目(CSTC2011jjA10004)

摘　　要：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.Objective： To observe the neuroprotective effect of OxAc on local cerebral ischemia in rats.Methods： The local cerebral ischemia/reperfusion model was established by intraluminal thread occlusion of the middle cerebral artery occlusion（MCAO） in rats.Fifty-four male SD rats were randomly divided into five groups： Sham group（n=6）,MCAO＋0.9%NS group（n=12）,MCAO＋OxAc group（n=12）,MCAO＋OxAc＋GOT group（n=12） and MCAO＋OxAc＋Maleate group（n=12）.Two hours after cerebral ischemia,various drugs were given,then glutamate concentration in serum,Longa scores,cerebral infarction volume and neuronal death measurement were used to assess the changes of ischemic brain tissues in different groups.Results： Two hours after MCAO,the cerebrospinal fluid glutamate levels in rats increased remarkably（p〈0.001）,but the plasma glutamate levels in rats did not change statistically.OxAc decreased the cerebrospinal fluid and plasma glutamate levels in cerebral ischemis rats rapidly and obviously（p〈0.05）.Compared with the MCAO＋0.9%NS group,OxAc intravenous injection increased the Longa scores（p〈0.05） and decreased the infarction volume（p〈0.01） and neuronal death number.Glutamate-oxaloacetate transminase（GOT） enhanced the effect of OxAc,but the specific inhibitor of GOT,maleate,attenuated the effect of OxAc.Conclusion： OxAc has a marked neuroprotective effect on local cerebral ischemia in rats,and this effect is related primarily to its blood glutamate scavenging activity.

关 键 词：草酰乙酸 谷氨酸 谷草转氨酶 缺血性脑卒中 

分 类 号：Q593[生物学—生物化学]