【摘要】 目的 运用网络药理学方法探讨泽泻汤治疗眩晕的作用机制。方法 在TCMSP数据库以泽泻、白术为关键词分别检索，按照OB>30%,DL>0.18的条件筛选，获得泽泻汤各中药的活性成分及其作用靶点；通过GeneCards、OMIM数据库检索眩晕的疾病靶点；确定泽泻汤与眩晕的交集基因，将预测到的成分及其疾病靶标运用Cytoscape软件进行药物-成分-疾病-靶点网络构建及分析，筛选核心靶点及主要活性成分，通过STRING数据库结合Cytoscape软件绘制蛋白相互作用（PPI）网络并进行网络拓扑学分析，通过R语言运行后对核心靶点进行GO分析和KEGG通路注释分析，设定阈值P<0.05,Q<0.05，筛选具有显著性差异的的生物学过程及信号通路。结果 筛选出泽泻汤17个成分和20个药物靶点；活性成分靶点与眩晕疾病靶点的交集基因共11个。其中，3β-乙酰氧基苍术酮（3β-acetoxyatractylone）、谷甾醇（Sitosterol）为核心化合物；毒蕈碱型乙酰胆碱受体M1(CHRM1)、毒蕈碱型乙酰胆碱受体M2(CHRM2)、糖皮质激素受体（NR3C1）、盐皮质激素受体（NR3C2）、孕酮受体（PGR）为关键靶点。GO分析结果显示，上述交集基因的分子功能主要包括G蛋白偶联受体活性、神经递质受体活性、核受体活性等。KEGG分析结果显示，生物学通路主要包括神经活性配体-受体相互作用通路、胆碱能突触、钙离子信号通路等。结论 本研究初步验证了泽泻汤治疗眩晕的药理学作用机制，揭示泽泻汤治疗眩晕通过核心靶点——CHRM1、CHRM2、NR3C1、NR3C2等参与神经活性配体-受体相互作用通路、胆碱能突触、钙离子信号通路的调控，可能通过调控交感神经系统，调节心率与平滑肌的收缩功能，减轻内耳炎症反应，调节内耳毛细胞的功能等发挥治疗眩晕症的目的。更多还原

【Abstract】 Objective To explore the mechanism of Ze Xie Decoction in treating vertigo through network pharmacology. Methods In TCMSP database, Zexie and Baizhu macrocephala were searched respectively, according to the conditions of OB>30% and DL>0.18, the active components and action targets of Zexie Decoction were obtained. The disease targets of vertigo were retrieved through GeneCards and OMIM databases. Next, we identified the intersection genes between Zexie Decoction and vertigo. The predicted components and their disease targets were used to construct and analyze the drug-component-disease-target network using the Cytoscape software. Core targets and main active components were screened. The protein-protein interaction(PPI) network was drawn using the STRING database in combination with the Cytoscape software and topological analysis was conducted. The core targets were analyzed using R language for GO analysis and KEGG pathway annotation analysis, with a threshold of P<0.05 and Q<0.05. Biological processes and signaling pathways with significant differences were screened. Results A total of 17 components and 20 drug targets of Zexie Decoction were screened. There are 11 intersection genes between active ingredient targets and vertigo disease targets. Among them, 3β-acetoxyatractylone and Sitosterol were the core compounds. Muscarinic acetylcholine receptor M1, muscarinic acetylcholine receptor M2, glucocorticoid receptor, salocorticoid receptor and progesterone receptor were the key targets. GO analysis results showed that the molecular functions of the above intersection genes mainly included G protein-coupled receptor activity, neurotransmitter receptor activity, and nuclear receptor activity. KEGG analysis showed that biological pathways mainly include neuroactive ligand-receptor interaction pathway, cholinergic synapse, calcium signaling pathway and so on. Conclusion This study preliminarily verified the pharmacological mechanism of Zexie Decoction in the treatment of vertigo. It is revealed that Zexia Decoction is involved in the regulation of neuroactive ligand-receptor interaction pathway, cholinergic synapse and calcium ion signaling pathway through core targets such as CHRM1, CHRM2, NR3C1 and NR3C2. The purpose of treating vertigo may be to regulate the sympathetic nervous system, regulate the heart rate and the contractile function of smooth muscle, reduce the inflammatory response of the inner ear, and regulate the function of the hair cells of the inner ear.更多还原