| 引用本文:王雪1，孙长岗2.青黛作用于急性幼粒细胞白血病的可视化“药靶蛋白模型”分析[J].世界中医药,2020,(12):. |
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| 青黛作用于急性幼粒细胞白血病的可视化“药靶蛋白模型”分析 |
| Analysis of Visible “Drug Target Protein Model” of Natural Indigo on Acute Promyelocytic Leukemia |
| 投稿时间：2020-03-02 |
| DOI：10.3969/j.issn.1673-7202.2020.12.004 |
| 中文关键词: 急性幼粒细胞白血病 青黛 药靶蛋白模型 靛玉红 靛蓝 基因 网络药理 生物信息 |
| English Keywords:Acute promyelocytic leukemia Natural Indigo Drug target protein model Indirubin Indigo Gene Network pharmacology Biological information |
| 基金项目:国家自然自然科学基金项目(81973677)——药物分子网络拟合模式指导下青黄散作用于急性早幼粒细胞白血病药靶蛋白机制的“分子动力-3D-QSAR”微观呈现;国家自然自然科学基金项目(81673799)——蛋白质相互作用网络与分子对接技术指导下青黄散对慢粒的作用机制研究;国家自然科学基金青年基金项目(8170141760)——基于“血清药物化学-计算机辅助分子预测-药靶蛋白协同”三维模式下青黄散治疗慢粒的配伍机制研究 |
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| 中文摘要: |
| 目的:目前青黛已是治疗急性幼粒细胞白血病(APL)的临床有效药物,但其分子机制与物质基础仍不明确。基于此本研究构建青黛与APL可视化药靶蛋白模型,以探究青黛作用于APL的分子机制。方法:通过GEO数据库检索APL微阵列芯片分析APL差异表达基因,使用TCMSP数据库筛选青黛活性成分,结合PubChem和SwissTargetPrediction匹配活性成分的靶基因并进行富集分析。String用于挖掘并构建APL可视化蛋白互作数据,将其读入Cytoscape,通过Centiscape实现网络拓扑分析。综合APL差异表达基因,通过Sybyl与青黛活性成分构建药靶蛋白模型。结果:筛选出3张APL微阵列芯片,164个差异表达基因,9种青黛活性成分,541个靶基因,这些靶点较多地参与细胞凋亡、药物结合、癌症途径、慢性粒细胞白血病等,这些都在APL中起重要作用。拓扑分析显示ELANE,CTSS为核心基因,将其与青黛9种活性成分进行药靶蛋白模型预测,显示靛玉红和靛蓝与核心基因结合度最佳。结论:APL是受多基因调控的复杂疾病,而青黛成分中靛玉红和靛蓝可通过结合ELANE,CTSS作用于APL的发生发展。 |
| English Summary: |
| At present, Natural Indigo has been used as a clinical drug for the treatment of acute promyelocytic leukemia(APL),but its effective molecular mechanism and material basis are still unclear. The purpose of this study is to construct the visible model of Natural Indigo and APL drug target protein, and to explore the molecular mechanism of Natural Indigo acting on APL. Methods:The APL microarray chip was searched through the GEO database to analyze the disease differentially expressed genes. The TCMSP database was used to screen the active ingredients of Natural Indigo. PubChem and SwissTarget Prediction were Combined to match target genes of active ingredients and enrichment analysis of target genes was done. String was used for further text mining and constructing a APL visual protein interaction network, the interaction data was read into Cytoscape, the network topology analysis was done through the plugin Centiscape. After comprehensive analysis of APL differentially expressed genes, Sybyl was constructed of drug target protein model with Natural Indigo active ingredients. Results:Three APL disease-related microarray chips, 164 differentially expressed genes, 9 Natural Indigo active components,541 component target genes were screened. These targets are more involved in apoptosis, drug combination, cancer pathway, chronic myelogenous leukemia, etc.,all of which play an important role in APL. Topological analysis showed that ELANE and CTSS were core genes, the drug target protein model prediction with the 9 active ingredients of Natural Indigo shows that indirubin and indigo have the best binding to core genes. Conclusion:APL is a complex disease regulated by multiple genes. The indirubin and indigo in Natural Indigo can act on the development of APL by combining ELANE and CTSS. |
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