Alterations of amino acid levels from striatum, hippocampus, and cerebral cortex induced by global cerebral ischemia in gerbil  

全脑缺血诱导沙土鼠纹状体,海马和皮层氨基酸水平的改变(英文)

作　　者：唐性春[1] 饶曼人[1] 胡刚[1] 汪海[2] 

机构地区：[1]南京医科大学生理学与药理学系 [2]军事医学科学院毒物药物研究所

出　　处：《Acta Pharmacologica Sinica》2000年第9期53-57,共5页中国药理学报（英文版）

基　　金：Project supported by State Key Project of New Drug Research and Developnment, No 969010101.

摘　　要：AIM: To investigate global cerebral ischemia-induced al-terations in the levels of glutamate, aspartate, γ-aminobutyric acid (GABA), glutamine, glycine, and taurine from hippocampus, striatum, and cerebral cortex in gerbils. METHODS: The gerbil global cerebral is-chemia model was prepared by bilateral carotid artery oc-clusion; the contents of amino acids were assayed using high performance liquid chromatography (HPLC) com-bined with fluorescent detection after precolumn derivati-zation. RESULTS: After the ligation of bilateral carotid artery for 5 min and reperfusion for 60 min, the contents of glutamate from hippocampus, striatum, and cortex in gerbils were increased by 40 % , 49 %, and 67 % , respectively. Similarly, the global cerebral is-chemia resulted in increase by 80 % , 69 % , and 83 % of aspartate contents in hippocampus, striatum, and cor-tex, respectively. Moreover, the same treatment also induced significant increases in the contents of GABA, glutamine, glycine, and taurine from various brain re-gions in gerbils. Furthermore, pretreatment with ke-tamine (120 mg/kg, ip) reversed ischemia-evoked in-creases of glutamate, aspartate, glycine, and glutamine in hippocampus, striatum, and cortex of gerbils. How-ever, administration of ketamine (120 mg/kg, ip) markedly suppressed but not abolished the ischemia-in-duced increases of taurine and GABA from hippocampus,striatum, and cortex in gerbils. CONCLUSION: The increases of glutamate, aspartate, glycine, and glutamine induced by acute global cerebral ischemia may constitute the biochemical basis of ischemic brain damage. Corre-spondingly, the release of GABA and taurine may be an important self-protective mechanism. Ketamine may protect neurons against ischemic insult by inhibiting glob-al cerebral ischemia-evoked increase of glutamate, glycine, and aspartate.目的:研究全脑缺血时沙土鼠海马、纹状体和皮层谷氨酸、天冬氨酸、γ-氨基丁酸(GABA)、谷氨酰胺、甘氨酸和牛磺酸含量的变化及氯胺酮对上述氨基酸含量的影响.方法:采用结扎双侧颈总动脉的方法制备沙土鼠全脑缺血模型,应用HPLC和荧光检测器联用测定氨基酸的含量.结果:全脑缺血显著增加沙土鼠海马,纹状体和皮层的谷氨酸,天冬氨酸,谷氨酰胺,GABA,甘氨酸和牛磺酸含量;氯胺酮(120 mg/kg,ip)预处理能完全逆转缺血诱导的谷氨酸、天冬氨酸、甘氨酸和谷氨酰胺释放的增加,但不能完全逆转缺血诱导的GABA和牛磺酸释放增加.结论:脑缺血诱发的神经元损伤可能与其增加谷氨酸、天冬氨酸、甘氨酸、谷氨酰胺含量有关,而抑制性氨基酸GABA和牛磺酸释放增加则可能是机体一种重要的自身脑保护机制.氯胺酮逆转脑缺血诱导的兴奋性氨基酸释放增加可能是其抗兴奋性神经毒的生化基础.

关 键 词：brain ischemia GERBILLINAE hippocam-pus corpus striatum cerebral cortex GLUTAMATES aspar-tate GAB A KETAMINE excitatory amino acids 

分 类 号：R743[医药卫生—神经病学与精神病学]