中文摘要：

目的：研究NMDA受体不同亚单位NR2A和NR2B分布与肌萎缩侧索硬化中运动神经元选择性易损的关系。方法：首先在离体培养的脑组织片中用谷氨酸转运抑制剂造成兴奋毒性损伤,观察在同等损伤条件下运动皮层和梨状区皮层是否出现有差异的神经元数量减少,然后用Western blot方法测定运动皮层和梨状区皮层的NR2A和NR2B的蛋白含量,证明选择性运动皮层损伤与NR2A和NR2B的不同分布方式有关,为进一步明确NR2A和NR2B在运动神经元谷氨酸慢性损伤中的作用不同,在离体培养的皮层运动神经元和脑组织片中分别抑制NR2A和NR2B,观察对运动神经元产生的影响。结果：用谷氨酸转运抑制剂THA100μmol/L损伤脑片2周后,运动皮层神经元的死亡率高于梨状区皮层,分别为64.50%±2.19%和30.43%±4.75%（P〈0.01）。Western blot结果表明NR2B/NR2A比值在运动皮层明显高于梨状区皮层,分别为0.87±0.09和0.47±0.09（P〈0.01）。抑制剂保护作用试验中,NR2B抑制剂显示出保护作用,离体培养的皮层运动神经元对照组、谷氨酸损伤组、谷氨酸＋NR2A抑制剂组和谷氨酸＋NR2B抑制剂组的运动神经元死亡率分别为6.85%±1.47%、47.48%±5.75%、45.76%±8.09%和18.10%±3.11%,脑片对照组、THA损伤组、THA＋NR2A抑制剂组和THA＋NR2B抑制剂组的运动神经元死亡率分别为12.49%±2.09%、100%、110.87%±15.76%和35.13%±5.32%。结论：NR2A和NR2B在运动神经元慢性谷氨酸损伤中所起的作用不同,NR2B在运动皮层的高分布造成肌萎缩侧索硬化中运动神经元的选择性易损。

英文摘要：

Objective：To investigate the relationship between different distribution of NMDA receptor subunits and motor neurons selective vulnerability in amyotrophic lateral sclerosis.Methods： First we investigated whether administration of THA,a glutamate transport inhibitor,in cultured organotypic brain tissue made different damage of motor cortex and piriform cortex.Then we testified that selective motor cortex injury was related to disparate distribution of NR2A and NR2B by measuring their protein expression with the method of Western blot.In order to make clear different role of NR2A and NR2B in chronic glutamate excitoto-xicity of motor neurons injury,we inhibited NR2A and NR2B separately in cultured cortical motor neurons and brain slices to investigate the mortality changes of motor neurons.Results： The mortality rate of neurons in motor cortex was apparently higher than that of piriform cortex（64.50%±2.19% and 30.43%±4.75%,P〈0.01） after cultured brain slices were damaged by THA 100 μmol/L for two weeks.Western blot results showed that protein expression of NR2B/NR2A ratio in motor cortex was prominently higher than that of piriform cortex（0.87±0.09 and 0.47±0.09,P〈0.01）.In inhibitor protective experiments,NR2B inhibitor showed positive effects.The mortality rates of cultured cortical motor neurons in control,glutamate,glutamate ＋ NR2A inhibitor,glutamate ＋ NR2B inhibitor were 6.85%±1.47%,47.48%±5.75%,45.76%±8.09%,18.10%±3.11%,respectively.The mortality rates of cultured motor cortex slices in control,THA,THA ＋ NR2A inhibitor,THA ＋ NR2B inhibitor were 12.49%±2.09%,100%,110.87%±15.76%,35.13%±5.32%,respectively.Conclusion： NR2A and NR2B subunits play different roles in motor neurons chronic glutamate excitoto-xicity.Intensive distribution of NR2B subunit in motor cortex makes motor neurons selectively vulnerable to glutamate excitotoxicity in amyotrophic lateral sclerosis.