虫类药治疗骨髓增殖性疾病的应用规律和作用机制探讨
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R27;R7.

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Study on Application Rule and Mechanism of Insect Medicinals for Myeloproliferative Diseases
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    目的:通过收集包含虫类药处方治疗骨髓增殖性疾病(MPD) 的文献,探讨虫类药治疗MPD的应 用规律和作用机制。方法:在中国知网(CNKI) 收集并筛选自建库起至202年12月期间在学术期刊发表的含 虫类药处方治疗MPD的文献,统计分析处方中虫类药的使用频次、四气五味、归经和毒性,并进行关联规则 分析,总结出虫类药治疗MPD的应用规律和核心药对。通过中药分子机制生物信息学分析工具(BATMANTCM) 检索,并结合现有文献筛选核心药对的活性成分和作用靶点。使用人类基因数据库(GeneCards)、在线 人类孟德尔遗传数据库(OMIM) 以及疾病相关的基因与突变位点数据库(DisGeNET) 检索MPD的疾病靶点。 将核心药对的作用靶点与疾病靶点取交集,并将核心药对的活性成分和交集靶点导入Cytoscape.9.1软件中进 行蛋白质相互作用(PPI) 网络构建分析,筛选核心成分。借助STRING数据库进行PPI网络构建,筛选核心靶 点。通过DAVID数据库对交集靶点进行基因本体(GO) 功能富集分析与京都基因与基因组百科全书(KEGG) 通路富集分析。将筛选出的核心成分与核心靶点进行分子对接。结果:收集到关于虫类药治疗MPD的文献共 166篇,其中水蛭的使用频次最高,共计10次。所用的虫类药,药性、药味主要为寒性、平性,咸味,归经 主要归肝经,毒性为无毒或有小毒。支持度最高的药物组合为水蛭-地龙。水蛭-地龙药对中有50个活性成分, 共对应585个作用靶点,与MPD的交集靶点有156个。筛选出的核心成分为熊果酸、花生四烯酸,核心靶点为 细胞肿瘤抗原p5(TP5)、RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)。GO功能富集分析结果主要涉及调控细 胞内关键过程、应对外来刺激、涉及分子间相互作用、维持细胞正常生理及对外界的适应性等,KEGG通路富 集分析结果主要涉及癌症、动脉粥样硬化及细胞凋亡等多条疾病相关通路。将筛选出的核心成分与核心靶点进 行分子对接,结果显示均有较好的结合活性。结论:水蛭-地龙主要通过熊果酸、花生四烯酸作用于TP5、 AKT1,并通过多条通路对MPD产生治疗作用。

    Abstract:

    Abstract: Objective: To investigate the application and mechanism of Insect medicinals in the treatment of myeloproliferative diseases (MPD) by collecting literatures containing Insect medicinals prescription. Methods: The literatures on the treatment of MPD with Insect medicinals published in academic journals from the self-established database to December 202 were collected and screened on CNKI. The frequency of use,four properties,five flavours, meridian tropism and toxicity of Insect medicinals in the prescription were statistically analyzed, and the association rules were analyzed to summarize the application rules and core drug pairs of Insect medicinals in the treatment of MPD. The active ingredients and action targets of the core drug pairs were screened by the A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) combined with the existing literature. Disease targets of MPD were searched using the Human Gene Database (GeneCards), the online Mendelian Inheritance in Man (OMIM), and the Disease-Associated Genes and Mutation Sites Database (DisGeNET). The target of the core drug pair was intersected with the disease target,and the active components of the core drug pair and the intersection targets were imported into Cytoscape.9.1 software for protein-protein interaction (PPI) network construction analysis, and the core components were screened. PPI network construction with STRING database,Screening core targets. The Gene Ontology( GO) function enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis were performed for the intersection targets using the DAVID database. Molecular docking was performed between the screened core components and the core target. Results: A total of 166 literatures on the treatment of MPD were collected,among which Hirudo were used the most frequently,10 times in total. The Insect medicinals used are mainly cold, neutral, salty, mainly liver channel, toxic is non-toxic or small. The drug combination with the highest support was Hirudo and Pheretima. There were 50 active ingredients in the pair, corresponding to a total of 585 action targets,and 156 intersection targets with MPD. The core components were ursolic acid and arachidonic acid,and the core targets were cell tumor antigen p5(TP5) and RAC-α serine/threonine protein kinase (AKT1). The results of GO functional enrichment analysis mainly involved the regulation of key cellular processes,response to external stimuli,involvement in molecular interactions,maintenance of normal cell physiology and adaptability to the outside world,etc. The results of KEGG pathway enrichment analysis mainly involved cancer, atherosclerosis, apoptosis and other disease-related pathways. The results of molecular docking between the selected core components and the core targets showed that all of them had good binding activity. Conclusion:Hirudo-Pheretima mainly acts on TP5 and AKT1 through ursolic acid and arachidonic acid, and exerts therapeutic effects on MPD through multiple pathways.

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马国栋,崔思远.虫类药治疗骨髓增殖性疾病的应用规律和作用机制探讨[J].新中医,2025,57(3):9-16

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  • 在线发布日期: 2025-02-22
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