谷氨酸载体在鼠脑缺血神经元死亡中的作用

Role of glutamate transporter in the pathogenesis of cerebral ischemia in rats

目的研究谷氨酸载体在脑缺血神经元死亡中的作用。方法用原位杂交和免疫组织化学方法观察大鼠脑缺血后脑内谷氨酸载体ＧＬＡＳＴｍＲＮＡ和胶质纤维酸性蛋白（ＧＦＡＰ）表达的变化，用药理分析手段观察谷氨酸载体摄取抑制剂Ｌ反式吡咯烷２，４二羧酸（ＬｔｒａｎｓＰＤＣ）对脑缺血致神经元损伤的影响。结果脑缺血后２４小时，大脑皮层缺血周边区ＧＬＡＳＴｍＲＮＡ和ＧＦＡＰ表达无显著变化；而缺血后７２小时，缺血周边区ＧＬＡＳＴｍＲＮＡ和ＧＦＡＰ表达都显著增加，脑缺血后２４小时和７２小时，缺血侧海马ＣＡ１区ＧＬＡＳＴｍＲＮＡ表达则无显著变化；与侧脑室注射生理盐水组相比，侧脑室注射１μｇ或２μｇＬｔｒａｎｓＰＤＣ有使脑梗塞体积增大的趋势，但差异无显著意义；侧脑室注射５μｇＬｔｒａｎｓＰＤＣ使脑梗塞体积显著增大。结论脑缺血后谷氨酸载体功能可能呈代偿性增强，提示谷氨酸载体在限制脑缺血时谷氨酸神经毒中起重要作用。

Objective To investigate the role of glutamate transporter in the pathogenesis of cerebral ischemia in rats.Methods In situ hybridization techniques of histochemistry and immunohistochemistry were used to observe the changes of glutamate/aspartate transporter messenger ribonucleic acid(GLAST mRNA) and glial fibrillary acidic protein (GFAP) expression in rat brains following focal cerebral ischemia.Pharmacological analysis technique was used to observe the effect of L trans PDC,a glutamate uptake inhibitor, on the infarction volume induced by photochemical focal cerebral ischemia. Results GLAST mRNA and GFAP expression in the area penumbra did not change 24h after ischemia, but increased significantly 72h following focal cerebral ischemia. No change in GLAST mRNA expression was noted in the ipsilateral hippocampal CA1 area following focal ischemia. In the rats pretreated with 1 μg or 2 μg L trans PDC adminstered into the lateral ventricles, there was a trend toward an increased infarction volume. Intraventricular injection of L trans PDC at a dose of 5 μg significantly increased the infarction volume. [WTHZ〗Conclusion The function of glutamate transporter might be enhanced following cerebral ischemia. Glutamate transporter might play an important role in limiting glutamate neurotoxicity under ischemic condition.