基于网络药理学的丹参川芎嗪注射液作用机制分析  

Mechanism analysis of Salviae Miltiorrhiza and Ligustrazine Hydrochloride Injection based on network pharmacology

作　　者：杨倩[1,2] 吕莉莉[3] 孙蓉[4,5] YANG Qian;LV Li-li;SUN Rong(Ri Zhao Hospital ofTCM, Rizhao 276800, China;Institute of Advanced Medical Science of Shandong University, Jinan 250012, China;The Second Hospital of Shandong University, Jinan 250033, China;Shandong Academy of Chinese Medicine, Jinan 250014, China;Shandong University of Traditional Chinese Medicine, Jinan 250355, China)

机构地区：[1]日照市中医医院,山东日照276800 [2]山东中医药大学,山东济南250355 [3]山东省中医药研究院,山东济南250014 [4]山东大学高等医学研究院,山东济南250012 [5]山东大学第二医院,山东济南250033

出　　处：《中草药》2018年第11期2606-2613,共8页Chinese Traditional and Herbal Drugs

基　　金：国家重大新药创制重大专项课题：中药复方药理学研究与药效评价关键技术(2009ZX09502-015); 山东省重大产业专项：国家基药大品种心可舒片二次深度开发(2015ZDZX07002); 泰山学者工程专项经费资助(Ns201511107)

摘　　要：目的探讨丹参川芎嗪注射液的药理作用机制。方法预测丹参川芎嗪注射液中已知化学成分的作用靶点,构建丹参川芎嗪注射液化合物-靶点网络,并对网络进行拓扑分析;对丹参川芎嗪作用靶点构建蛋白互作网络(PPI),进行基因GO功能注释和KEGG通路富集分析,预测丹参川芎嗪注射液的药理作用机制,并通过丹参川芎嗪注射液预处理对脑缺血大鼠海马MAPK表达的影响初步验证其作用机制。结果丹参川芎嗪注射液中15个主要化合物作用于94个靶点蛋白,PRSS1、PTGS2、F2、PTGS1是化合物-靶点网络中的关键节点蛋白。PPI网络包含71个靶蛋白,关键蛋白涉及SRC、MAPK-1、MMP-9、MAPK-14、PTGS2、BCL-2等;PPI网络中的靶蛋白富集在26条GO功能和6条主要的KEGG通路中。结论本研究结果预测了丹参川芎嗪注射液广泛药理学作用的机制,并对其治疗脑缺血的作用机制进行了初步验证,为进一步深入研究丹参川芎嗪注射液的药理作用机制、发现新的治疗作用及靶点提供参考。Objective To investigate the efficacy and mechanism of Salviae Miltiorrhiza and Ligustrazine Hydrochloride Injection（SMLHI）. Methods The targets of chemical components of SMLHI were predicted and the compounds-targets（C-T） network was constructed. The key targets were screened through the topology analysis of the C-T network. Also, protein-protein interaction（PPI） network was established, and the Gene ontology and KEGG pathway was enriched and analyzed. The pharmacological action mechanism of SMLHI was predicted, and the mechanism was preliminarily verified by pretreating with SMLHI on the MARK expression of cerebral ischemia rats. Results Fifteen main compounds in SMLHI act on 94 targets and PRSS1, PTGS2, F2, and PTGS1 were key targets in the C-T network. There were 71 targets in the PPI network including several key nodes such as SRC, MAPK-1, MMP-9, MAPK-14, PTGS2, BCL-2, and so on. All the targets were enriched in 26 GO items and six KEGG pathways. Conclusion Results in this study preliminarily verified the action of SMLHI on cerebral infarction and diabetic peripheral neuropathy, thus laying a solid foundation for further study on the mechanism of action.

关 键 词：丹参川芎嗪注射液 蛋白相互作用关系 网络药理学 富集分析 靶点 

分 类 号：R285.5[医药卫生—中药学]