c-fos反义寡核苷酸对谷氨酸神经毒性鼠脑损伤的防护  

Protective effect of c-fos antisense oligonucleotides on brain damage induced by glutamate

作　　者：岳少杰[1] 陶永光[1] 罗自强[2] 冯德云[3] 伍赶球[4] 

机构地区：[1]中南大学湘雅医学院湘雅医院儿科,长沙410008 [2]中南大学湘雅医学院生理教研室 [3]中南大学病理教研室 [4]中南大学组胚教研室

出　　处：《中华医学杂志》2001年第3期145-149,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目! (3 970 0 193 )

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Ca2 + 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 .0 1) ,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 .0 1)、钠(5 .0 5mg/g干重± 0 .39mg/g干重和 5 .98mg/g干重± 0 .5 0mg/g干重 ,P <0 .0 1)及细胞内Ca2 + (176nmol/L± 35nmol/L和 34 4.12± 5 0 .13,P <0 .0 1)含量的增加 ,抑制谷氨酸所致大脑皮质 (15 7± 10和 145± 7,P <0 0 1)及海马CA1区 (2 97.6 4± 18.3和 2 10± 19,P <0 .0 1)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cObjective 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.

关 键 词：谷氨酸盐类 脑损伤 C-FOS基因 反义寡核苷酸 神经毒性 

分 类 号：R651.15[医药卫生—外科学]