世界中医药

目的：基于生物信息学方法对糖尿病脑病（DE）的关键基因进行初步筛选，探索与其相关的潜在靶点、生物过程及通路，进而预测治疗DE的潜在中药。方法：运用GEO数据库筛选出基因芯片原始数据集GSE161355作为样本进行研究。基于R Studio软件的质量评估和差异分析筛选差异基因，应用DAVID数据库进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析，利用Cytoscape软件进行关键靶点筛选及关键功能模块构建、可视化。通过将关键靶点与Coremine Medical数据库相互映射，筛选治疗DE的潜在中药。结果：通过对GSE161355基因原始数据集的预处理，从DE患者中筛选出326个显著性差异基因，差异基因主要参与学习、记忆、神经元突触传递、细胞分裂、蛋白质分泌、血管生成调节等生物过程，与神经活性配体-受体信号通路、细胞周期通路等存在关联。蛋白质-蛋白质相互作用（PPI）网络显示MCHR2、CXCR2、GNAI1、P2RY13、NPY1R、C3、LPAR4、OXTR、CHRM5、CDC7、ORC5、ORC4、CCNA1可作为治疗DE的潜在靶点，多方位、多维度、多层面参与炎症反应、细胞凋亡、内质网应激、血管生成等生物过程。通过中药预测筛选发现人参、熟地黄、西红花、银杏叶、黄连、郁金等可作为潜在来源。结论：通过对显著性差异基因和潜在核心靶点的分析促进了对DE发病机制的进一步理解和探索，为今后治疗和评估提供了新的方向和临床依据。

English Summary:

This study aims to screen key genes related to diabetic encephalopathy(DE)，potential targets of the genes，and biological processes and pathways of the genes based on bioinformatics，and thereby predict potential effective Chinese medicinals.Methods:The microarray dataset GSE161355 was screened from Gene Expression Omnibus(GEO) for analysis.Differently expressed genes were yielded based on quality evaluation and difference analysis by R Studio，and DAVID was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.Cytoscape was applied to screen key targets and visualize key functional modules.By mapping key targets with the Coremine Medical，we screened potential Chinese medicinals for the treatment of DE，and constructed the “potential medicinal-active component-core target” network.Results:A total of 326 significantly differential genes were screened out，which were involved in the biological processes such as learning，memory，synaptic transmission of neurons，cell division，protein secretion，and angiogenesis regulation，and the pathways of neural active ligand-receptor interaction，cell cycle，and other pathways.The protein-protein interaction(PPI) network showed MCHR2，CXCR2，GNAI1，P2RY13，NPY1R，C3，LPAR4，OXTR，CHRM5，CDC7，ORC5，ORC4，and CCNA1 were potential targets against DE，which were involved in inflammation，cell apoptosis，endoplasmic reticulum stress，angiogenesis，and other biological processes from multiple aspects.Radix Ginseng，Radix Rehmanniae Preparata，Stigma Croci，Folium Ginkgo，Rhizoma Coptidis，and Radix Curcumae were effective medicinals，which nourish qi，blood，yin and yang，promote blood circulation，remove blood stasis，dredge collaterals，resolve phlegm，refresh the brain，and resuscitate.Conclusion:This study further clarified the pathogenesis of DE through the analysis of differentially expressed genes and potential core targets，which provides a new theoretical research direction and clinical basis for future treatment and prognosis evaluation.

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