茯苓甘草汤治疗肺动脉高压机制探讨  

Therapy Mechanism of Fuling Gancao Decoction on Pulmonary Hypertension based on Network Pharmacology and Molecular Docking

作　　者：马雨婷 司明东 张笑迎 贾毓欣 闫翠环[1] 马东来[1] MA Yuting;SI Mingdong;ZHANG Xiaoying;JIA Yuxin;YAN Cuihuan;MA Donglai(Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation of Hebei University of Chinese Medicine Hebei Shijiazhuang 050200,China)

机构地区：[1]河北中医学院河北省中药组方制剂技术创新中心,河北石家庄050091

出　　处：《中医药临床杂志》2022年第4期675-682,共8页Clinical Journal of Traditional Chinese Medicine

基　　金：河北省自然科学基金项目(H2021423013);河北省第二期现代农业产业技术体系创新团队项目(HBCT2018060205);河北省大学生创新创业训练项目(202014432022)。

摘　　要：目的:该文通过网络药理学方法研究茯苓甘草汤治疗肺动脉高压(PH)的作用机制。方法:在中药系统药理学分析平台(TCMSP)中寻找并筛选与茯苓甘草汤的化学成分和作用靶点,通过数据库筛选肺动脉高压相关的靶点,获得化合物-疾病共同作用靶基因,进而构建“药物-化合物-靶点”相互作用网络图和蛋白质互作网络图并进行拓扑分析;对核心靶点进行GO分析,利用KEGG数据库对核心靶点进行相关通路富集,并构建“靶点-通路”网络。将“药材-化合物-靶点”网络中排名前15的成分与血管细胞黏附分子-1(VCAM-1)和细胞间黏附分子-1(ICAM-1)进行分子对接。结果:该文筛选出茯苓甘草汤119个活性成分和90个相应靶点;通过网络拓扑特征评价筛选出与茯苓甘草汤在肺动脉高压方面作用核心靶点11个,如EGFR、CTNNB1、UBC等。GO功能富集分析得到GO条目1419个(P≤0.05),其中生物过程(BP)条目1251个,细胞组成(CC)条目55个,分子功能(MF)条目113个。KEGG通路富集筛选得到119条信号通路(P≤0.05)。分子对接结果显示shinpterocarpin、7-Methoxy-2-methyl isoflavone、3’-Methoxyglabridin、β-sitosterol、Licoagrocarpin等核心活性化合物与VCAM-1和ICAM-1的亲和力较好。结论:通过网络药理学证实了茯苓甘草汤多靶点、多成分、整体调节的作用特点,预测了茯苓甘草汤治疗肺动脉高压的主要可能作用机制,验证了网络药理学的预测结果,综合阐释了其抗PH的作用机制,为今后的分子生物学实验奠定了理论基础。Objective:To study the mechanism of Fuling Gancao decoction in the treatment of pulmonary hypertension(PH)by means of network pharmacology.Methods:The chemical constituents and action targets of Fuling Gancao decoction were searched and screened in the Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP),and the targets related to pulmonary arterial hypertension were screened through the database to obtain compound-disease co-acting target genes,and then construct Drug-compound-target interaction network diagram and protein interaction network diagram and perform topology analysis;GO analysis is performed on the core target,and the KEGG database is used to enrich the relevant pathways of the core target,and construct a“target-pathway”.The internet Molecular docking of the top 15 components of the“Medicinal-Compound-Target”network with Vascular Cell Adhesion Molecule-1(VCAM-1)and Intercellular Adhesion Molecule-1(ICAM-1).Results:In this paper,119 active ingredients and 90 corresponding targets of Fuling Gancao decoction were screened out;11 core targets,such as EGFR,CTNNB1,UBC,etc.,were screened out by Fuling Gancao Decoction in pulmonary hypertension through the evaluation of network topology.GO functional enrichment analysis yielded 1419 GO entries(P≤0.05),including 1251 biological process(BP)entries,55 cellular composition(CC)entries,and 113 molecular function(MF)entries.KEGG pathway enrichment screening yielded 119 signaling pathways(P≤0.05).Molecular docking results showed that the core active compounds,7-Methoxy-2-methyl isoflavone,3’-Methoxyglabridin,β-sitosterol,Licoagrocarpin had better affinity with VCAM-1 and ICAM-1.Conclusion:The multi-target,multi-component,and overall regulation of Fuling Gancao decoction was confirmed by network pharmacology,the main possible mechanism of Fuling Gancao decoction in the treatment of pulmonary hypertension was predicted,the prediction results of network pharmacology were verified,and a comprehensive explanation was given.Its anti-PH

关 键 词：茯苓甘草汤 肺动脉高压 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]