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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 intravenous oxaloacetate (OxAc) on focal cerebral ischemia in rats.Methods: The middle cerebral artery occlusion (MCAO) 54 male SD rats were randomly divided into 5 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) .After ischemia for 2h, different drugs were injected intravenously immediately after reperfusion to detect the volume of glutamate (Glu) in serum and cerebrospinal fluid Neurobehavioral score, cerebral infarction volume and neuron loss.Results: After 2h of cerebral ischemia, the content of Glu in the cerebrospinal fluid increased significantly (p <0.001), and the content of Glu in the plasma had no significant difference (P <0.05). Compared with MCAO + 0.9% NS group, the application of OxAc can significantly increase the level of Glu in the plasma and cerebrospinal fluid of cerebral ischemia rats Behavioral score (p <0.05) decreased the volume of cerebral infarction (p <0.01), and significantly improved the neuronal loss in the relevant brain regions of rats. When GOT was injected intravenously, the effect of OxAc could be promoted, while maleate, a GOT-specific inhibitor, could reduce the effect of OxAc.Conclusion: Acute focal cerebral ischemia has obvious neuroprotective effects, and this effect is mainly achieved through its use as a “glutamate scavenger” in the bloodstream.