【摘要】 目的:比较Aβ处理前后大鼠额叶皮质的基因表达谱差异,探讨β-淀粉样蛋白(Aβ)神经毒性的分子机制。方法:应用含有4200条大鼠基因的cDNA表达谱芯片对Aβ1-40诱导后的大鼠额叶皮质进行基因表达谱分析。结果:芯片杂交结果分析显示,Aβ1-40诱导组和生理盐水对照组额叶皮质间的差异表达基因共46个,包括上调基因18个,下调基因28个。Go Miner软件对差别表达基因生物学功能的分类结果显示这些基因主要与细胞信号传导、细胞增殖与生长、免疫反应、细胞粘附、离子通道和能量代谢等功能有关。结论:Aβ通过多种途径和机制触发和诱导了神经元的变性,我们的结果为进一步阐明阿尔茨海默病的分子机理提供了一些新的线索。更多还原

【Abstract】 Objective: Many studies have suggested the involvement of amyloid E-protein (AB) for neuronal cell death, However, the molecular mechanism of the pathogenesis is still unclear. The aim of this study was to investigate the molecular events underlying the Al3 induced neuronal impairment in rat cortex. Methods: Fluorescence-labeled cDNA probes generated from Aβ_ 1-40 treated rat cortex (cy5) and control cortex (cy3) were co-hybridized with a DNA microarray containing 4200 rat genes. After hybridization, slides were scanned and the results were analyzed by GoMiner software package. Results: Of the 4,200 genes and expressed sequence tags analyzed, a group of 46 genes with altered expression were identified in Aβ_ 1-40 treated rat cortex. Comparison: of expression levels revealed that 18 genes were up-regulated (>2 fold) and 28 genes were down-regulated (<0.5 fold) by a treatment with Aβ_ 1-40. This differential expression profile included genes encoding proteins involved in the function of signal transduction, cell growth and/or maintenance, inflammation, regulation of transcription, apoptosis, cell motility, ion channel and neurotransmitter transporter. Conclusion The broad spectrum of the differentially expressed genes indicated an overall cellular response upon Aβ_ 1-40 treatment. Our result should provide a deeper insight into the molecular mechanism of Alzheimer’s disease.更多还原