大鼠脑缺血再灌注损伤期间脑组织间质各种氨基酸递质水平的变化

Changes in amino acid neurotransmitters during cerebral ischemia and reperfusion in awake rats

目的 :研究清醒大鼠脑缺血再灌注损伤期间海马、纹状体和新皮质细胞外多种氨基酸递质水平的变化。方法 :复制清醒大鼠前脑缺血模型 ,利用微透析技术 ,于缺血前、缺血 15min、再灌注 15min、30min、6 0min、12 0min及 180min时所收集透析液 ,测定谷氨酸、天门冬氨酸、γ -氨基丁酸、甘氨酸、牛磺酸、丙氨酸、谷氨酰胺、丝氨酸、苏氨酸等 9种氨基酸含量 ;并计算缺血再灌注期间不同脑区兴奋毒性指数 (EI)的变化。结果 :缺血期间细胞外液中不仅兴奋性氨基酸如谷氨酸、天门冬氨酸等以及兴奋性氨基酸受体调质如甘氨酸显著增高 ,而且抑制性氨基酸如γ-氨基丁酸及抑制性氨基酸受体调质如牛磺酸和丙氨酸亦明显升高 ;但是反映兴奋性神经递质与抑制性神经递质平衡综合指数的EI值在缺血期间明显升高。结论 :脑缺血期间单纯谷氨酸、天门冬氨酸等升高可能不足以造成缺血性损伤 ,其它神经递质或其它因素协同兴奋性氨基酸在介导神经细胞内一系列病理生化反应而引起延迟性神经细胞损伤的过程中可能起重要作用。

AIM: To study the dynamic changes of amino acid neurotransmitters during cerebral ischemia and reperfusion in awake rats. METHODS: Model of cerebral ischemia and reperfusion in awake rats was replicated. Glutamate (Glu), aspartate (Asp), γ-aminobutyric acid (GABA), glycine (Gly), taurine (Tau), alanine (Ala), serine (Ser), threonine (Thr) and glutamine (Gln) concentrations were measured with microdialysis, and excitotoxic index (EI) was calculated in dialysates of hippocampus, neo-cortex and striatum. RESULTS: The significant increases in extracellular not only excitatory amino acid neurotransmitters-Glu and Asp, and their neuromodulator-Gly, but also inhibitory amino acid neurotransmitter-GABA and its neuromodulator-Tau and Ala were observed. However, the EI, representing the balance of excitatory and inhibitory neurotransmitters, was significantly increased during ischemia. CONCLUSION: The results suggest that the elevated Glu and Asp levels during ischemia are insufficient to independently engender ischemic damage, and other neurotransmitters or other factors may play an important role in modulating the excitotoxic effects of Glu and Asp.