摘要
目的 为进一步探讨星形胶质细胞在癫痫发病中的作用。方法 选用肿瘤坏死因子 α (tumornecrosisfac tor α ,TNF α)刺激及TNF α反义寡核苷酸阻断后马桑内酯 (coriarialactone ,CL)刺激纯化培养的海马星形胶质细胞 ,将上述两种条件培养基提取液 (astrocyticconditionedmedium ,ACM) 10 μl分别注入正常Sprague Dawley (SD)大鼠侧脑室 ,观察动物行为与脑电图的变化 ;用免疫细胞化学方法检测大脑皮质与海马中γ 氨基丁酸 (gamma aminobu tyricacid ,GABA)表达水平的改变 ,并做显微图像分析。 结果 ①侧脑室注射TNF α刺激后的条件培养基提取液可引起大鼠Ⅲ级癫痫样发作及典型的尖波、棘波、棘 慢波癫痫样脑电图表现 ,大鼠大脑前梨状皮质和海马齿状回GA BA免疫反应阳性神经元数和平均吸光度值均明显低于对照组 ;②侧脑室注射TNF α反义寡核苷酸阻断后由马桑内酯刺激的条件培养基提取液 ,大鼠无癫痫样行为发生 ,大鼠大脑前梨状皮质和海马齿状回GABA免疫反应阳性神经元数和平均吸光度值与对照组无显著性差异。结论 ①激活的星形胶质细胞分泌的TNF α可诱导大鼠癫痫发作。②GABA表达的变化可能与癫痫发作有关。
Objective To investigate the role of astrocytes in epileptogenesis. Methods After the purified culture astrocytes were stimulated by the TNF-α or coriaria lactone (CL), which were used following the pretretement of TNF-αantisense oligodeoxynucletide, the astrocyte conditioned media (ACM) were collected. Then 10 μl of these ACM were injected into lateral cerebroventricule of normal Sprague-Dawley (SD) rats. The changes of animal behavior and EGG were observed. The changes in the expression of gamma-aminobutyric acid (GABA) in cerebral cortex and hippocampus were studied by immunocytochemical method and microimage assay. Results The third grade epileptic behavior was induced after injecting the ACM, which confirmed by shape, spike and spike-slow waves on EGG. The average optical density and the number of GABA-positive cells in cerebral cortex and the area dentate was significantly decreased after injection as compared with the control group. No epileptic behaviors were observed after injecting the media blocked by TNF-antisense oligodeoxynucleotide and then stimulated by CL into the lateral ventricle. There was no significant difference in average optical density and the number of GABA-positive cells in cerebral cortex and the area dentate between the experimental group and control group. Conclusion TNF-αsecreted by activated astrocytes could induce the seizure of rats. The change in the expression of GABA might by closely related to epileptic actions.
出处
《华中科技大学学报(医学版)》
CAS
CSCD
北大核心
2004年第4期388-392,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目 (No 39970 379)