局灶性皮质发育不良基因表达及相关信号通路分析  

The analysis of gene expression profile and related signal pathways in focal cortical dysplasia

作　　者：华立栋 李文斌[1] 高曲文[2] 隋立森[3] 范翠霞[1] 欧阳小明[4] 廖卫平[1] 黎冰梅[1] 石奕武[1] 

机构地区：[1]广州医科大学附属第二医院神经致病基因与离子通道病省部共建教育部重点实验室,510260 [2]广州军区广州总医院癫痫科,510010 [3]广东省中医院,广州市510120 [4]广州医科大学附属第二医院病理科,510260

出　　处：《实用医学杂志》2016年第3期347-351,共5页The Journal of Practical Medicine

基　　金：广州市科技计划项目(编号:2014J4100069);广东省医学科研基金项目(编号:A2013268);首都医科大学省部级重点实验室开放研究课题(编号:2014DXBL04)

摘　　要：目的:利用基因表达谱芯片研究局灶性皮质发育不良(FCD)病变组织和正常脑组织中差异表达的基因,探讨FCD可能的发病机制。方法:收集FCD患者病变脑组织(病例组)及正常人(对照组)脑组织各3例,抽提总RNA,利用Affymetrix基因表达谱芯片分析病例组与对照组差异表达的基因;Real-time q PCR验证芯片结果;生物信息学分析差异表达基因参与的相关信号通路,预测FCD可能的致病机制。结果:通过对FCD组织和正常脑组织的基因表达谱的比较分析,发现在FCD组织中C21or F2、AU152162表达上调,ENPP2、ANLN、IP6K3、UGT8、AZGP1表达下调。Real-time qPCR验证表明,ENPP2、ANLN、IP6K3、UGT8、AZGP1基因在病例组和对照组中的表达差异具有统计学意义(P<0.05)。生物信息学分析表明,ENPP2、UG T8、AZGP1蛋白定位于细胞膜或者分泌到细胞外基质,可能通过涉及到脂质代谢以及溶血磷脂酸(LPA)信号通路途径参与髓鞘的形成和神经系统的发育。结论:ENPP2、UGT8、AZGP1基因表达下调,可能通过影响髓鞘的形成及LPA信号通路参与FCD的发生,这些基因参与FCD发生的具体致病机制有待进一步研究。Objective To investigate the potential pathogenesis of Focal cortical dysplasia （FCD）, we performed eDNA mieroarray analysis to obtain gene expression profile of FCD. Methods Three FCD samples and three normal controls were enrolled. Total RNA of the brain tissues were extracted. The difference gene expressions between FCD group and control group was detected using Affymetrix gene chip. The up and down- regulated genes were confirmed by Real-time PCR. Further, the related signal pathways involved in the pathogenic mechanisms of FCD were predicted by bioinformatics. Result In FCD, two up-regulated genes C21orF2 and AU152162 and 5 down-regulated genes ENPP2, ANLN, IP6K3, UGTS, and AZGP were found. Compared the FCD samples with the normal controls, there were significantly different in all down-regulated genes （P 〈 0.05）, while the up-regulated genes were not （P 〉 0.05）. Using bioinformatics analysis, the ENPP2, UGT8, and AZGP1 protein which located in the cell membrane or secreted into the extracellular matrix may be involved in the formation of the myelin sheath and the development of the nervous system by the lipid metabolism and LPA signaling pathway. Conclusion ENPP2, UGT8 and AZGP1 may be involved in pathogenesis of FCD through the process of myelin sheath formation and LPA signal pathway, which warrants further study to know their roles in the pathogenesis of FCD.

关 键 词：局灶皮质发育不良 基因表达 溶血磷脂酸 信号通路 髓鞘 

分 类 号：R742.8[医药卫生—神经病学与精神病学]