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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。
OBJECTIVE: To study the differential expression of Notch signaling pathway-related genes in degenerative ganglion and surrounding brain tissues of human cerebral arteriovenous malformations (BAVM) using gene chip. Methods: Five cases of BAVM with hemorrhagic history were collected and collected from the deformity mass and the surrounding brain tissue. Notch signaling pathway gene chip hybridization was performed to obtain the numerical signal intensity of each gene point on the gene chip, and the mean and standard deviation were calculated. Calculate the ratio of abnormal gene cluster chip and surrounding brain tissue on the chip. Take the ratio> 1.5 or <0.67 factor, summed up the expression of significant differences in the gene. Two of these genes were validated by realtime PCR. RESULTS: Of the 113 Notch signaling pathway genes, 27 significantly altered genes were screened out, of which 4 were up-regulated and 23 down-regulated. The more important genes include Notch signaling pathway ligands DLL1, DLL3, receptor and ligand cleavage key genes ADAM10, ADAM17, Notch signaling pathway target gene HES5, Notch related Sonic Hedgehog pathway gene GLI1, Wnt signaling pathway gene FZD1, proto-oncogene Gene LMO2. Realtime PCR verified DLL1 and HES5 two genes, the test results and chip results are basically consistent. Some Notch signaling pathway key gene expression in two parts of no difference. Conclusion: Multiple Notch signaling pathway genes are differentially expressed in the BAVM malformations and surrounding brain tissues, suggesting that the occurrence and development of BAVM are related to the Notch signaling pathway. Peripheral brain tissue, the Notch signaling pathway may also be abnormal. Differentially expressed genes can be used as BAVM further study of the entry point.