益气活血方治疗高原红细胞增多症的作用机制及关键microRNA筛选研究  

Study on the Mechanism and Key MicroRNAs Screening of Yiqi Huoxue Recipe in Treating High Altitude Polycythemia

作　　者：吕李飞 杨如意[2] 赵成周 贾守宁[4] 祁永福[4] LV Lifei;YANG Ruyi;ZHAO Chengzhou;JIA Shouning;QI Yongfu(Qinghai Provincial Key Laboratory of Traditional Chinese Medicine Research for Glucolipid Metabolic Diseases,Qinghai University,Xining 810016,China;Affiliated Hospital of Qinghai University,Xining 810001,China;Tibetan Medicine College,Qinghai University,Xining 810001,China;Qinghai Provincial Hospital of Traditional Chinese Medicine,Xining 810012,China)

机构地区：[1]青海大学青海省糖脂代谢疾病防控中医药重点实验室,青海西宁810016 [2]青海大学附属医院,青海西宁810012 [3]青海大学藏医学院,青海西宁810001 [4]青海省中医院,青海西宁810012

出　　处：《高原科学研究》2023年第1期81-91,共11页Plateau Science Research

基　　金：青海省卫生健康委员会重点项目(2020-wjzd-11);青海省重点研发与转化科技合作专项(2019-HZ-819);青海省高层次卫生人才(领军人才)项目(2018年、2019年);青海省中藏医药科研创新项目(J2020005)。

摘　　要：目的基于网络药理学及分子对接技术,预测益气活血方治疗高原红细胞增多症的核心物质和作用机制,筛选出其关键的microRNA,为中医药治疗高原红细胞增多症提供数据与方向。方法通过TCMSP和ETCM数据库筛选益气活血方潜在活性成分及作用靶点;GeneCards数据库、NCBI数据库、OMIM数据库获取HAPC疾病靶点;Venny在线平台进行交集靶点分析;利用STRING数据库及R语言、Cytoscape软件对交集靶点进行蛋白相互作用分析、GO功能和KEGG通路富集分析,采用Cytoscape构建“靶点-通路”网络模型,借助Autodock Vina进行有效成分与核心靶点的分子对接验证;采用TargetScan和miRDB数据库对核心基因进行microRNA预测。结果共筛选出方药潜在活性成分143个和330个药物靶点;得到方药治疗高原红细胞增多症的潜在作用靶点34个;核心靶点为AKT1、ALB、VEGFA、IL6、NOS3,主要参与的关键通路为HIF-1信号通路、VEGF信号通路、p53信号通路;分子对接显示baicalein-NOS3的对接分值最低,结合效果好;进一步得出miR-15b-5p、miR-4307、miR-29a-3p等关键调控microRNA。结论初步揭示了益气活血方干预高原红细胞增多症可能是通过多成分、多靶点、多途径发挥防治作用。Objective Based on network pharmacology and molecular docking technology,the core substances and mechanism of action of Yiqi Huoxue Recipe in the treatment of High Altitude Polycythemia(HAPC)were pre-dicted,and its key microRNA was screened out,providing the basis and direction for the further research on tra-ditional Chinese medicine in the treatment of HAPC.Methods The potential active components and action tar-gets of Yiqi Huoxue recipe were screened through TCMSP and ETCM databases;Obtained HAPC disease targets from GeneCards database,NCBI database and OMIM database;performed intersection target analysis using Ven-ny online platform;conducted protein-protein interaction analysis,GO function and KEGG pathway enrichment analysis on the intersection targets using STRING database,R language and Cytoscape software;built a"target-pathway"network model using Cytoscape;verified the molecular docking between the active ingredient and the core target using Autodock Vina;and predicted microRNA of core genes using TargetScan and miRDB databas-es.Results A total of 143 potential active ingredients and 330 drug targets were screened out;34 potential tar-gets of the prescription for treating high altitude polycythemia were obtained;The core targets are AKT1,ALB,VEGFA,IL6 and NOS3,mainly through HIF-1 signaling pathway,VEGF signaling pathway and p53 signaling pathway;Molecular docking showed that baicalein-NOS3 had the lowest docking score and good binding effect;It was further concluded that miR-15b-5p、miR-4307、miR-29a-3p and other key regulatory microRNAs.Con-clusion It is preliminarily revealed that the intervention of Yiqi Huoxue Recipe on high altitude polycythemia may play a preventive and therapeutic role through multi-component,multi-target and multi-channel mecha-nisms,which can provide a basis and direction for follow-up experimental research.

关 键 词：益气活血方 高原红细胞增多症 作用机制 MICRORNA 

分 类 号：R285.5[医药卫生—中药学]