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基于网络调控探讨黄芪-川芎药对治疗缺血性脑卒中的作用机制及配伍效应

[Mechanism and compatibility efficacy of Astragali Radix-Chuanxiong Rhizoma drug pair in treating ischemic stroke based on network regulation].

作者信息

Li Zhuo-Hang, Qi Ming-Zhu, Huang He-Lan, Su Xiao-Hui, Kong Xiang-Ying

机构信息

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2024 May;49(9):2326-2335. doi: 10.19540/j.cnki.cjcmm.20231225.402.

Abstract

Based on the association network of "drug pair-disease", the effect characteristics of Astragali Radix-Chuanxiong Rhizoma drug pair in the treatment of ischemic stroke(IS) with Qi deficiency and blood stasis and the matching mechanism of the two were explored. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction Database, the effective chemical components of the drug pair were screened, and the candidate targets were predicted. Databa-ses such as GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD) were searched to obtain gene targets related to IS. Through STRING and Cytoscape 3.9.1 software, the protein-protein interaction(PPI) network was constructed by using the interaction information of disease syndrome-related genes and candidate targets of drug pairs, and the core targets were screened according to the network topological feature values. Based on the Metascape platform and DAVID database, the biomolecular interaction information was integrated to analyze the Kyoto Encyclopedia of Genes and Genomes(KEGG) and mine biological functions, so as to further explore the mechanism of action and compatibility characteristics of Astragali Radix-Chuan-xiong Rhizoma. The results showed that the candidate biological process was mainly involved in the regulation of functional modules such as immune, blood circulation, neurotransmitter, and oxidative stress, and it was enriched in lipid and atherosclerosis, calcium signaling pathway, and platelet activation. Astragali Radix and Chuanxiong Rhizoma have their own characteristics. Astragali Radix has a regulatory response to growth factors while maintaining the body's immune balance, while Chuanxiong Rhizoma mainly improves the circulatory system and participates in hormone metabolism, so as to indicate the compatibility mechanism of Astragali Radix-Chuanxiong Rhizoma drug pair for multi-target and multi-pathway synergistic treatment of IS. Through further experimental verification, it was found that the Astragali Radix-Chuanxiong Rhizoma drug pair could significantly down-regulate the expression of key targets including TLR4, NF-κB, IL-1β, F2R, PLCβ1, and MYLK. This study preliminarily reveals that the Astragali Radix-Chuanxiong Rhizoma drug pair may play the three replenishing effects of promoting blood circulation, benefiting Qi, and clearing collaterals by correcting immune di-sorders, blood circulation disorders, and inflammation, which provide support for the clinical research on the subsequent improvement of Qi deficiency and blood stasis in the treatment of IS and provide a new idea for the analysis of modern biological connotation of the compatibility of seven emotions of traditional Chinese medicine.

摘要

基于“药对-疾病”关联网络,探讨黄芪-川芎药对治疗气虚血瘀型缺血性脑卒中(IS)的效应特点及二者的配伍机制。通过中药系统药理学数据库与分析平台(TCMSP)和瑞士靶点预测数据库,筛选药对的有效化学成分,预测候选靶点。检索基因卡片(GeneCards)、药物银行(DrugBank)、人类孟德尔遗传在线数据库(OMIM)和治疗靶点数据库(TTD)等数据库,获取与IS相关的基因靶点。利用STRING和Cytoscape 3.9.1软件,根据疾病证候相关基因与药对候选靶点的相互作用信息构建蛋白质-蛋白质相互作用(PPI)网络,并依据网络拓扑特征值筛选核心靶点。基于Metascape平台和DAVID数据库,整合生物分子相互作用信息,分析京都基因与基因组百科全书(KEGG)并挖掘生物学功能,以进一步探究黄芪-川芎的作用机制及配伍特点。结果表明,候选生物学过程主要涉及免疫、血液循环、神经递质和氧化应激等功能模块的调控,且富集于脂质与动脉粥样硬化、钙信号通路和血小板活化。黄芪和川芎各有特点。黄芪对生长因子有调节反应,同时维持机体免疫平衡,而川芎主要改善循环系统并参与激素代谢,从而揭示黄芪-川芎药对多靶点、多途径协同治疗IS的配伍机制。通过进一步实验验证,发现黄芪-川芎药对可显著下调包括TLR4、NF-κB、IL-1β、F2R、PLCβ1和MYLK等关键靶点的表达。本研究初步揭示,黄芪-川芎药对可能通过纠正免疫紊乱、血液循环障碍和炎症发挥活血化瘀、益气通络的三重功效,为后续IS治疗中改善气虚血瘀的临床研究提供支持,并为分析中药七情配伍的现代生物学内涵提供新思路。

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