Notch信号通路基因在人脑动静脉畸形和周围脑组织中的差异表达  

Differential Notch Signalling Pathway Gene Expression of Nidus and Adjacent Brain Tissure Parts in Human Brain Arteriovenous Malformations

作　　者：郑名哲[1] 陈衔城[1] 汤海亮[1] 谢清[1] 宫晔[1] 

机构地区：[1]复旦大学附属华山医院神经外科,200040

出　　处：《中国临床神经科学》2012年第6期625-631,共7页Chinese Journal of Clinical Neurosciences

摘　　要：目的:应用基因芯片研究人脑动静脉畸形(BAVM)的畸形团及周围脑组织的Notch信号通路相关基因的差异表达。方法:收集有出血史的5例BAVM标本,在畸形团、周围脑组织分别取材,进行Notch信号通路基因芯片杂交,得到基因芯片上各基因点数值型信号强度,计算其均数和标准差。计算畸形团芯片及周围脑组织芯片上各基因点的比值。取比值>1.5或<0.67的因子,归纳总结出表达水平有明显差异的基因。以realtime PCR方法对其中任意选取的2个基因进行验证。结果:在113个Notch信号通路基因中,共筛选出27个明显变化的基因,其中,上调4个,下调23个。较为重要的基因包括Notch信号通路配体DLL1、DLL3,受体及配体裂解关键基因ADAM10、ADAM17,Notch信号通路靶基因HES5,Notch相关的Sonic Hedgehog通路基因GLI1、Wnt信号通路基因FZD1、原癌基因LMO2。realtime PCR验证DLL1和HES5两个基因,其检测结果与芯片结果基本相符。部分Notch信号通路关键基因在两个部位表达无差异。结论:多个Notch信号通路基因在BAVM畸形团及周围脑组织存在差异表达,提示BAVM的发生发展与Notch信号通路有关。周围脑组织中,Notch信号通路亦可能存在异常。差异表达的基因可作为BAVM进一步研究的切入点。Aim： To investigate the expression of genes involved in Notch signalling pathway of different parts in human brain arteriovenous malformations （BAVM） by using Notch signalling pathway microarray. Methods： Five BAVM cases with stroke history were collected, whose sample of nidus （N） and adjacent brain fissure （B） were obtained in surgery. Signal intensity of the genes was examed and calculated by using Oligo GE Array Human Notch Signaling Pathway Microarray OHS-059. The genes with N/B ratio larger than 1.5 or smaller than 0.67 were counted as markablly changed, two of which were verified by realtime PCR. Results： Twenty seven of 113 genes involved in Notch signalling pathway were found differentially expressed. Four genes were up- regulated, and twenty three genes were down-regulated. Most important genes include Notch signalling pathway ligands DLL1/DLL3, key genes of cleavage ADAMIO/ADAM17, Notch signalling pathway target gene HES5,Notch related Sonic Hedgehog pathway gene GLI1, Wnt signalling pathway gene FZD 1, oncogene LM02. The data from two genes DLL1 and HES5 by realtime PCR is basically consisted with the data from the gene chip. Some important genes involved in Notch signalling pathway did not show differential expression at the two parts of BAVM. Conclusion： Many of the genes involved in Notch signalling pathway were differential expressed at nidus and adjacent brain tissue parts in BAVM, which indicated BAVM occurrence and developing have something to do with Notch signalling pathway. Notch signallling pathway gene expression pattern might be different at adjacent brain tissure. Differential expressed genes can contribute new ways to BAVM research.

关 键 词：脑动静脉畸形 脑组织 NOTCH信号通路 基因芯片 

分 类 号：R739.41[医药卫生—肿瘤]