基于网络药理学与分子对接技术探讨藏族药佐木阿汤治疗高血压病的作用机制  

Study on mechanism of Tibetan medicine Zuomua Decoction in treatment of hypertension based on network pharmacology and molecular docking technology

作　　者：贡巴加 任越 马婧 更桑 多杰仁青 李贡宇[1] 尼玛次仁 张燕玲[1] GNG Ba-jia;REN Yue;MA Jing;GENG Sang;DUO Jie-ren-qing;LI Gong-yu;NI Ma-ci-ren;ZHANG Yan-ling(Beijing University of Chinese Medicine,Beijing 102488,China;Tibetan Traditional Medical College,Lasa 850000,China;Tha Xi Ke Community Health Serice Center in Yushu,Yushu 815000,China)

机构地区：[1]北京中医药大学,北京102488 [2]西藏藏医药大学,西藏拉萨850000 [3]青海省玉树市扎西科社区卫生服务中心,青海玉树815000

出　　处：《中国中药杂志》2020年第22期5383-5392,共10页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2017YFC1704001)。

摘　　要：高血压病是由一系列因子和载体发生功能障碍而引起的一种慢性心血管系统疾病,属于藏族医"查隆病"的范畴,具有较高的致残率、致死率。佐木阿汤是藏族医中用于治疗"查隆病"的经典方药,然而其作用机制尚不清晰。因此该研究利用网络药理学与分子对接技术探讨佐木阿汤治疗高血压病多成分、多靶标、多通路的作用机制。首先,研究通过中药系统药理学数据库(TCMSP)、中国知网以及万方数据库检索获得佐木阿汤的化学成分,利用BATMAN-TCM数据库筛选获取佐木阿汤的潜在作用靶点集,借助DisGeNET数据库收集高血压疾病靶点集,取2个靶点集交集获得佐木阿汤治疗高血压病的潜在作用靶点,并构建化学成分-靶点网络。其次将交集靶点导入STRING数据库中获得交集靶点互作关系并在Cytoscape中构建佐木阿汤治疗高血压病的蛋白互作网络。利用拓扑、GO、KEGG富集分析构建关键靶点-信号通路-生物过程网络图,共同探讨佐木阿汤治疗高血压病的作用机制。最后选取关键靶点构建药效辨识模型以验证佐木阿汤治疗高血压病的作用模式。研究结果显示佐木阿汤治疗高血压病的化合物-靶点网络中共包含61个化学成分与90个潜在作用靶点。对佐木阿汤治疗高血压病的蛋白互作网络分别进行拓扑、KEGG、GO富集分析,共获得21个佐木阿汤治疗高血压病的关键靶点,154条信号通路,382条生物学过程,对关键靶点、信号通路、生命过程进行综合分析,发现佐木阿汤通过调节肾素-血管紧张素-醛固酮系统、平衡细胞内钙和钠离子的浓度、调节血管收缩舒张功能发挥降压作用。以ACE,AGTR1和ADRB2为研究载体,对佐木阿汤化学成分进行分子对接研究,结果显示佐木阿汤化学成分与关键靶点具有较好的结合活性。该研究旨在为佐木阿汤治疗高血压病的深入研究提供思路,并为其临床合理应用提供�Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein intera

关 键 词：网络药理学 分子对接 佐木阿汤 高血压病 查隆病 作用机制 ACE AGTR1 ADRB2 

分 类 号：R285[医药卫生—中药学]