谷氨酸转运抑制剂对大鼠培养脑片皮层锥体细胞的影响  

Effects of glutamate transporter inhibitor on rat cortical pyramidal cells in organotypic cultured brain slices

作　　者：肖向建[1] 刘卫刚[1] 李敏[1] 马征[1] 李春岩[1] 

机构地区：[1]河北医科大学第二医院神经内科

出　　处：《基础医学与临床》2006年第1期51-54,共4页Basic and Clinical Medicine

基　　金：河北省自然科学基金(303487)

摘　　要：目的观察谷氨酸转运抑制剂苏-羟天冬氨酸(THA)对大鼠培养脑片中大锥体细胞的影响,探讨谷氨酸在皮层运动神经元损伤中的作用。方法取出生后1 d SD乳鼠的运动区大脑切片培养,用含有不同浓度THA的培养液进行干预,培养后的脑片用神经元特异性免疫组化染色剂SMI-32(抗非磷酸化神经丝抗体)染色,对皮层大锥体细胞进行鉴定、计数,透射电镜观察超微结构,并测定不同时点培养液中谷氨酸(Glu)的含量。结果对照组脑片大锥体细胞数目稳定,而THA可以引起剂量依赖性培养液中Glu含量的升高及大锥体细胞数目减少,空泡变性。结论细胞外谷氨酸增高对大锥体细胞造成慢性损伤。Objective This study aimed at the effect of glutamate（Glu） on rat cortical pyramidal cells in cultured brain slices treated by threohydroxyaspartate （THA）, an inhibitor of glutamate transporter. Methods The brain slice cultures were prepared using 1-day-old rat. Various concentrations of THA（50,100 and 500 μmol/L）were added into the culture medium respectively. Cortical pyramidal cells＇ survival was evaluated by immunohistochemistry staining monoclonal antibody SMI-32, a nonphosphorylated neurofilament marker, Glu level in the culture medium was also measured. Ultrastructural picture of neuropathology were examined by EM microscopy. Results The brain slices in the control group maintain excellent organization and a stable population of pyramidal cells. THA caused a slow dose-dependent loss of cortical pyramidal cells and an increase of Glu level in the culture medium. THA of 100 μmol/L resulted in a significant decrease in cortical pyramidal cells after culturing for 5 weeks. Pyramidal cells appeared vacuolar degeneration. Condnsions Extra-cellular Glu caused chronic excitotoxicity to cortical pyramidal cells.

关 键 词：脑片 大锥体细胞 谷氨酸 肌萎缩侧索硬化 大鼠 

分 类 号：R965[医药卫生—药理学]