伽玛刀对颞叶癫痫模型大鼠基因差异表达的影响

Effects of gamma knife on gene expression of animal model for temporal lobe epilepsy in rat

目的分析正常-癫痫-伽玛刀治疗过程中起核心调控作用的基因及其涉及的功能和信号转导途径，从基因表达水平探讨伽玛刀治疗癫痫的机制。方法应用立体定向技术建立大鼠颞叶癫痫模型，进行伽玛刀照射，提取海马RNA进行芯片杂交、清洗、染色和扫描，获取芯片数据。基于芯片数据对正常-癫痫-伽玛刀治疗进行差异基因筛选，分析基因表达趋势，并对差异基因进行功能及信号转导通路分析，构建目标趋势的动态差异基因的共表达调控网络，从网络中得到正常-癫痫-伽玛刀治疗过程中起核心调控作用的基因群体。结果按照1．5倍法筛选得到正常．癫痫-伽玛刀治疗3组间并集差异基因766个，这些差异基因涉及离子转运（P=6．85×10^-24）、细胞黏附（P=1．55×10^-8）、机械刺激反应（P=7．86×10^-7）、钾离子转导（P=2．63×10^-6）等生物功能及MAPK信号通路（P=5．55×10“）、钙离子信号通路（P=4．29×10^-5）、TGF-13信号通路（P〈0．01）等信号转导途径，共表达网络分析得到的核心调控基因包括Arf3、Akap5、Omd、Rtn4r等。结论伽玛刀通过调节具有不同功能、介导不同信号转导途径的靶基因实现其对颞叶癫痫大鼠的治疗作用。．

Objective To explore the core controlling genes and their functions and pathways of gamma knife in the treatment of epilepsy in rats. Methods The temporal epilepsy rats induced by stereotaetie technique were irradiated with gamma knife. Total RNA samples were isolated at 3 weeks post- irradiation. After hybridization, washing and staining, the probe arrays were scanned to acquire the gene chip data. The functional categories and affected pathways of differentially regulated genes were analyzed. And the gene co-expression network was constructed to determine the core controlling genes. Results The differentiated genes of normal, epileptic and epileptic rats treated with gamma knife were screened by 1.5- fold method. There were a total of 766 union genes. The differentiated up-regulated and down-regulated genes were obtained. These genes were involved in functional categories such as ion transport （ P = 6. 85 × 10^ -24 ）, cell adhesion （P = 1.55 × 10 ^-8 ）, response to mechanical stimulus （P =7.86 × 10^ -7 ）, potassium ion transport （ P = 2. 63 × 10 ^-6 ） and such pathways as MAPK signaling （ P = 5.55 × 10^ -6 ）, calcium signaling （P =4. 29 × 10 ^-5 ） and TGF-beta signaling （P 〈0. 01 ）, etc. And the core controlling genes from the gene co-expression network included Arf3, Akap5, Omd and Rtn4r, etc. Conclusion Gamma knife achieves its antiepileptic effect through modulating target genes involved in different functions and pathways.