【摘要】
目的：探讨c-fos基因的表达在谷氨酸神经毒性中的作用。

方法：在9只SD大鼠侧脑室注射c-fos反义寡核苷酸以阻断脑组织c-fos基因的表达，并用c-fos正义寡核苷酸为对照。观察脑组织中水、电解质含量和突触体内Ca-2+浓度的变化，并采用细胞形态计量分析及免疫组织化学方法，观察大脑皮质、海马CA1区神经细胞数目、形态的变化及c-fos基因的表达。

结果：c-fos反义寡核苷酸可有效地阻断脑组织c-fos基因的表达，降低脑组织c-fos阳性细胞率（9.4%±2.8%和74%±3%，P＜0.01＝，抑制谷氨酸神经毒性所致的脑组织含水量（79.9%±0.4%和82.3%±0.8%，P＜0.01＝、钠（5.05 mg/g干重±0.39 mg/g干重和5.98 mg/g干重±0.50 mg/g干重，P＜0.01＝及细胞内Ca-2+（176 nmol/L±35 nmol/L和344.12±50.13，P＜0.01＝含量的增加，抑制谷氨酸所致大脑皮质（157±10和145±7，P＜0.01＝及海马CA1区（297.64±18.3和210±19，P＜0.01＝神经细胞的丢失，减轻神经细胞的形态学损伤。C-fos正义寡核苷酸无此效应。

结论：c-fos基因的表达在谷氨酸神经毒性脑损伤的发生中起有重要作用，阻断c-fos基因的表达可以拮抗谷氨酸神经毒性。

【关键词】 谷氨酸盐类； 脑损伤； 基因，fos

Protective effect of c-fos antisense oligonucleotides on brain damage induced by glutamate
YUE Shaojie*, LUO Ziqiang, FENG Deyun, et al.*Department of Pediatrics，Xiangya Hospital，Xiangya Medical College of Zhongnan University，Changsha 410008, China

【Abstract】 Objective To investigate the relation between glutamate neurotoxicity and c-fos gene expression. Methods c-fos antisense oligonucleotides (AS ODN) was injected into the right lateral ventricles of 9 SD rats to block the c-fos gene expression in brain tissue. C-fos sense oligonucleotides （S ODN）was used a control. The numbers and morphology of neurons in both cerebral cortex and hippocampal CA1 were detected by MIAS-300 image analysing instrument. C-fos gene expression in brain was observed by immunohistochemical method. The content of water and electrolytes in the brain tissue and Ca-2+in the synapse were measured. Results The c-fos AS ODN blocked the c-fos gene expression and reduced the content of both water and sodium in brain tissue and Ca-2+in symptosome, thus alleviating the morphological damage in neuron. S ODN did not have such effect. Conclusion c-fos gene expression plays an important role in mediating the effect of glutamate neurotoxicity. Blocking the c-fos gene expression could antagonize glutamate neurotoxicity.

【Key words】 Glutamates； Brain injuries； Genes, fos

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