基于数据挖掘及网络药理学探讨胡晓梅主任治疗真性红细胞增多症的用药规律及机制

Research on prescription regulation and mechanisms of Dr HU Xiaomei in the treatment of polycythemia vera based on data-mining and network pharmacology

关键词:  真性红细胞增多症  中医传承辅助系统  网络药理学  胡晓梅

Key words:  polycythemia vera  traditional Chinese medicine inheritance support system  network pharmacology  HU Xiaomei

摘要:

[目的] 基于数据挖掘和网络药理学方法，探讨胡晓梅主任治疗真性红细胞增多症的用药规律及其作用机制，为真性红细胞增多症的治疗提供新思路。[方法] 通过回顾性研究方法，收集2018年4月1日—2020年11月30日胡晓梅主任治疗真性红细胞增多症（PV）的有效方剂202首，通过中医传承辅助平台（V2.5）软件分析其处方的用药规律，通过频次分析筛选累计频次最高的前10味中药作为其治疗本病的核心药物。然后对核心药物进行了网络药理学分析，探索其治疗PV的潜在的分子机制。[结果] 通过药物频次分析得到的前10位的核心药物是生地黄、柴胡、白花蛇舌草、赤芍、龙葵、半枝莲、龙胆、夏枯草、黄芩、牛膝。用药模式分析结果显示最常见的核心组合是生地黄和柴胡。网络药理学分析结果显示核心药物的靶点为378个，与PV相关的疾病靶点为589个，韦恩图显示核心药物与PV相关的靶点为114个。基因本体论（GO）富集分析显示核心药物治疗PV主要涉及氧化应激、药物反应及细胞凋亡等生物过程，它们通过细胞因子受体-配体结合、磷酸化作用、血红素结合、蛋白结合、激酶调节等分子功能在细胞膜、分泌囊泡等部位发挥作用。京都基因与基因组百科全书（KEGG）富集于PI3K-Akt、HIF-1、JAK-STAT、P53等信号通路。蛋白互作网络图显示，STAT3、AKT1、TP53、MAPK1、TNF、VEGFA、MAPK14、IL6有可能是核心药物治疗PV的关键靶点。[结论] 运用数据挖掘和网络药理学分析方法，获得胡晓梅主任治疗PV的高频核心药物，并揭示了核心药物具有多成分、多靶点、多通路治疗PV的潜在作用机制，为临床治疗PV提供了参考方案，并为进一步深入的物质基础和分子机制研究提供了思路。

Abstract:

[Objective] Based on data-mining and network pharmacology methods,to explore the prescription pattern and its pharmaceutical mechanism of chief physician Dr HU Xiaomei in polycythemia vera (PV),and to provide new ideas for the treatment of PV. [Methods] Through a retrospective study method,202 effective prescriptions of HU Xiaomei for the treatment of PV from April 31,2018 to November 30,2020 were collected. The dosing regulation of her prescriptions was analyzed by traditional Chinese medicine inheritance support system (V2.5),and the top 10 herbs with higher cumulative frequency were screened by frequency analysis as core drugs for the disease. Then the core drugs were analyzed by network pharmacology to explore the underlying molecular mechanisms. [Results] The top 10 core drugs obtained by drug frequency analysis were rehmannia glutinosa libosch,radix bupleuri,herba hedyotis,radix paeoniae rubra,solanum nigrum linn,scutellariae barbatae herba,gentianae radix et rhozima,prunellae spica,scutellariae radix and achyranthis bidentatae radix. The results of the dosing pattern analysis showed that the most common couplet medicine were rehmannia glutinosa libosch and radix bupleuri. The results of network pharmacology analysis showed 378 targets of core drugs and 589 disease targets associated with PV,and the Venn diagram showed 114 targets of core drugs associated with PV. GO enrichment analysis showed that core drugs for PV mainly involve biological processes such as oxidative stress,drug response and apoptosis,which are mediated through cytokine receptor-ligand binding,phosphorylation,and heme binding. The functional location included cellular membrane and secretory cysts. KEGG is enriched in PI3K-Akt,HIF-1,JAK-STAT,P53 and other signaling pathways. The protein-protein interaction network map showed that STAT3,AKT1,TP53,MAPK1,TNF,VEGFA,MAPK14,and IL6 were likely to be the key targets for core drug treatment of PV. [Conclusion] Using data-mining and network pharmacology analysis,we obtained the high-frequency core drugs for the treatment of PV by chief physician HU Xiaomei,and revealed the potential pharmaceutical mechanism of the core drugs with multi-component,multi-target and multi-pathway against PV,which provided a reference scheme for the clinical treatment of PV and ideas for further study of the material basis and molecular mechanism.