基于网络药理学探讨真武汤治疗慢性心力衰竭的作用机制

目的: 通过网络药理学的方法探讨真武汤治疗慢性心力衰竭(chronic cardiac failure，CHF) 的作用机制。方法: 通过中药网络药理学分析平台(TCMSP)获取真武汤中候选化合物，利用Swiss Target Prediction平台,进行候选靶标预测，并将TCMSP中相应化合物的靶点作为补充，利用Uniprot数据库将靶点蛋白转化成基因名；通过CTD和TTD数据库获取CHF的相关基因，将真武汤靶标(基因)与CHF相关基因取交集作为真武汤治疗CHF的潜在靶标，将交集基因提交至STRING11.0在线数据库进行蛋白互做分析，并借助网络可视化软件 Cytoscape 3. 7. 1绘制蛋白相互作用网络图，利用Excel构建真武汤中药-潜在化合物-潜在靶标网络，并利用Cytoscape 3. 7. 1进行可视化；通过RStudio的clusterProfiler包进行通路富集分析。结果: 通过设置OB和DL值筛选得到真武汤汤化合物59种，在获得交集基因36个后，剔除不含交集基因（靶标）的化学成分后，最终筛得化合物49种，KEGG富集分析共获得36条，其中13条与CHF相关。结论: 去甲乌头碱、3β-乙酰氧基苍术酮、山奈酚、芍药苷、豆甾醇、β-谷甾醇等为真武汤主要活性成分，白介素6、内皮型一氧化碳合酶、血红素加氧酶1 、前列腺素G/H合酶2、过氧化氢酶等为主要作用靶标，主要调控环鸟苷酸-蛋白激酶G信号通路、肾素分泌、钙信号通路等通路。本研究初步明确了真武汤通过多成分-多靶点-多通路治疗CHF的作用机制, 为深入研究真武汤的药效物质基础和作用机制奠定基础。

Study on the Mechanism of Zhenwu Decoction in Treating Chronic Heart Failure Based on Network Pharmacology

Obeject: Discuss the action mechanism of chronic cardiac failure (CHF) treated with zhenwu decoction through network pharmacology.Method: Candidate compounds in zhenwu decoction were obtained through the network pharmacology analysis platform (TCMSP). Swiss Target Prediction platform was used to predict candidate targets, The targets of the corresponding compounds in TCMSP were supplemented. Uniprot database was used to convert target proteins into gene name. Genes related to CHF were obtained by CTD and TTD databases, Taking the intersection of zhenwu decoction target (gene) and chf-related gene as the potential target of zhenwu decoction in the treatment of CHF. The intersection gene was submitted to STRING11.0 online database for protein interchange analysis, The network diagram of protein interaction was drawn by using network visualization software Cytoscape 3. 7. 1. Using Excel, the network of zhenwu decoction - potential compound - potential target was constructed, Cytoscape 3. 7. 1 was used for visualization. Path enrichment analysis was performed through RStudio''s clusterProfiler package. Results: Fifty-nine compounds of zhenwu decoction were screened by setting OB and DL values. After 36 intersection genes were obtained and chemical components without intersection genes (targets) were eliminated, 49 compounds were finally screened. A total of 36 articles were obtained by KEGG enrichment analysis, 13 of which were related to CHF.Conclusion: Deoxyaconitine, 3 beta-acetoxyatractylone, kaempferol, paeoniflorin, Stigmasterol and beta-sitosterol are the main active ingredients of genwu decoction, IL6, NOS3, HMOX1, PTGS2 and CAT are the main targets, main control cGMP - PKG signaling pathway, Renin secretion and Calcium signaling pathway. This study preliminarily clarified the mechanism of zhenwu decoction in treating CHF through multi-component, multi-target and multi-pathway therapy, laying a foundation for further study on the pharmacodynamics basis and mechanism of zhenwu decoction.