基于网络药理学的益气活血蠲毒法治疗尿毒症心肌病的机制研究

Mechanism Analysis of Therapy of Replenishing Qi,Activating Blood and Eliminating Toxicity in Treatment of Uremic Cardiomyopathy Using Network Pharmacology

目的运用网络药理学的方法探讨益气活血蠲毒法治疗尿毒症心肌病(UCM)的作用机制。方法通过TCMSP平台获取益气活血蠲毒法的主要活性成分,利用PubChem平台、Swiss Target Prediction平台收集药物靶标基因,通过人类基因数据库(GeneCards)获得UCM相关的靶标基因,采用String数据库和Cytoscape软件分析蛋白相互作用网络,通过Systems Dock Web Site对成分与关键靶标基因进行分子对接验证。借助Cytoscape对关键靶标基因进行GO分析和KEGG通路分析,并构建成分关键靶标基因-通路-疾病网络。结果筛选得到益气活血蠲毒法42个活性成分,涉及28个关键作用靶标基因。网络分析结果表明,靶标基因主要涉及活性氧的代谢过程、与物质跨膜运动相关的ATP酶活性等生物过程,通过调节MAPK信号通路、ABC转运蛋白、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路、抗叶酸剂、色氨酸代谢、类固醇生物合成等信号通路发挥治疗UCM的作用。结论研究结果初步预测了益气活血蠲毒法对UCM的基本药理基础及作用机制,益气活血蠲毒法治疗UCM具有多基因参与的特点,可能与减少尿毒症毒素蓄积,抑制炎症及氧化应激水平有关。

Objective To explore the mechanism of therapy of replenishing Qi,activating blood and eliminating toxicity in the treatment of uremic cardiomyopathy(UCM) by the network pharmacology.Methods The main active ingredients of therapy of replenishing Qi,activating blood and eliminating toxicity were obtained through TCMSP.The platforms of PubChem and Swiss Target Prediction were used to obtained drugs’ target genes.Relevant target genes of UCM were obtained through GeneCards.The protein interaction network was constructed using the String database and Cytoscape software.The relation between the main active ingredients and key target genes was validated by Systems Dock Web Site.The GO and KEGG pathways involved in the key target genes were analyzed by Cytoscape software.The ingredients-key target gene-pathways-diseases network was constructed by Cytoscape software.Results The results showed that 42 active components and 28 key target genes oftherapy of replenishing Qi,activating blood and eliminating toxicity were involved.The network results showed that the process of reactive oxygen species biosynthetic,ATPase activitycoupled to transmembrane movement of substanceswere mainly involved,which played a role in the treatment of UCM by adjusting MAPK,ABC transporters,PI3 K-Akt,Antifolate resistance,Tryptophan metabolism,Steroid hormone biosynthesis and other signal pathways.Conclusion The results of this study preliminarily predicted the basic pharmacological basis and mechanism of therapy of replenishing Qi,activating blood and eliminating toxicity on UCM.Therapy of replenishing Qi,activating blood and eliminating toxicity in the treatment of UCM has the characteristics of multi-gene participation,which may be related to uremia toxin storage reducing and inhibition of oxidative stress level.