Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology
Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology
复制标题
网络药理学揭示中药治疗房颤合并阻塞性睡眠呼吸暂停低通气综合征的协同机制
DOI：
10.1155/2019/8691608
复制
发表时间：
2019-12-24
影响因子：
--
通讯作者：
Zhang, Shan
中科院分区：
文献类型：
--
作者：
Mao, Ting;Zhang, Jingchun;Zhang, Shan
阵发性房颤(房颤)合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)在临床上十分常见。中医心机治肝法治疗阵发性房颤合并阻塞性睡眠呼吸暂停低通气综合征疗效满意。然而，其潜在的药理机制尚未阐明。本研究应用网络药理学从多个数据库和综合文献研究中筛选出6种调肝中药中的94种有效成分和182个相应靶点，并结合OSAHS相关靶点检索AF。采用Cytoscape软件构建成分-成分靶点网络和成分推定靶点-AF结合OSAHS靶点网络。在此基础上，我们获得了38个与OSAHS联合治疗房颤的潜在靶点。在构建可能的治疗靶点相互作用网络后，采用拓扑分析的方法确定中医调肝中药治疗阵发性房颤合并OSAHS的核心靶点。针对所有可能的治疗指标，采用生物过程分析和途径浓缩分析，探讨调肝中药治疗阵发性房颤合并OSAHS的可能机制。从机制上讲，它包括对一氧化氮生物合成过程、衰老、低氧反应、肿瘤坏死因子信号通路、HIF-1信号通路、PI3K-Akt信号通路、神经活性配体-受体相互作用和钙信号通路的正向调节。其中，肿瘤坏死因子、STAT3、AKT1、IL-6、TP53、INS等6个调肝中药核心靶点在上述生物学过程和途径的调控中具有重要意义。本研究揭示了调肝中药的多组分、多靶点、多途径的特点，为进一步的研究提供了可拓的基础，促进了调肝中药在治疗阵发性房颤合并OSAHS中的合理应用。
Paroxysmal atrial fibrillation (AF) combined with obstructive sleep apnea hypopnea syndrome (OSAHS) is very common in clinical practice. Traditional Chinese medicine (TCM) rule of regulating the liver based on psycho-cardiology shows satisfactory effectiveness in the treatment of paroxysmal AF combined with OSAHS. However, its underlying pharmacological mechanism has not yet been elucidated. This study applied network pharmacology to identify 94 active components in the six TCM liver-regulating herbs and 182 corresponding targets from several databases and comprehensive literature studies, as well as retrieved AF combined with OSAHS-related targets. Cytoscape software was adopted to construct the component-component target network and component-putative target-AF combined with OSAHS target network. Then, we obtained 38 putative therapeutic targets against AF combined with OSAHS. After the production of a putative therapeutic target interaction network, topological analysis was adopted to determine the core targets of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. For all putative therapeutic targets, biological process analysis and pathway enrichment analysis were utilized to investigate the possible mechanism of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. Mechanistically, it included positive regulation of nitric oxide biosynthetic process, aging, response to hypoxia, TNF signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and calcium signaling pathway. Especially, six core targets of TCM liver-regulating herbs, namely, TNF, STAT3, AKT1, IL-6, TP53, and INS, were significant in the regulation of the above biological processes and pathways. This study demonstrates the multicomponent, multitarget, and multipathway feature of TCM liver-regulating herbs, provides an extensional foundation for further research, and facilitates the reasonable application of TCM liver-regulating herbs in treating paroxysmal AF combined with OSAHS.