基于网络药理学和分子对接的脑泰方防治高血压脑小血管病作用机制研究  

Study on the Action Mechanism of Naotaifang in the Prevention and Treatment of Hypertensive Cerebral Small Vessel Disease Based on Network Pharmacology and Molecular Docking

作　　者：林宏远 方锐[1] 张泽鑫 周月 王珊珊[1] 蒋祁零 宋祯彦[1] 梅志刚 葛金文[1,3] 商洪才 Lin Hongyuan;Fang Rui;Zhang Zexin;Zhou Yue;Wang Shanshan;Jiang Qiling;Song Zhenyan;MeiZhigang;Ge Jinwen;Shang Hongcai(College of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Shaoyang University,Shaoyang 422000,China;Dozhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]湖南中医药大学中西医结合学院,长沙410208 [2]广州中医药大学第一临床医学院,广州510405 [3]邵阳学院,邵阳422000 [4]北京中医药大学东直门医院,北京100700

出　　处：《世界科学技术-中医药现代化》2021年第12期4364-4373,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家科学技术部国家重点研发计划(2018YFC1704904):脑泰方防治高血压脑小血管病变的循证优化研究,负责人:葛金文;湖南省科学技术厅省重点研发计划(2022SK2016):高血压脑小血管病中西医结合诊疗的循证优化研究,负责人:葛金文;湖南中医药大学校级科研基金项目(2020XJJJ025):内质网线粒体偶联在高血压脑小血管病内皮细胞损伤中的作用及脑泰方干预机制研究,负责人:方锐。

摘　　要：目的运用网络药理学和分子对接方法,探讨脑泰方防治高血压脑小血管病(Hypertensive cerebral small vessel disease,HT-CSVD)的作用机制。方法首先,利用中医药数据库及分析平台(TSMSP)、中药分子机制的生物信息学分析工具(BATMAN-TCM)与中医药资料库@Taiwan,并结合相关文献筛选脑泰方的主要有效活性成分,再经PubChem数据库与Swiss Target Prediction数据库预测其潜在靶点。其次,通过Genecards与在线人类孟德尔遗传(OMIM)数据库分别筛选出高血压和脑小血管病相关靶点,其交集靶点作为HT-CSVD的相关靶点。再次,利用Cytoscape 3.7.2软件构建“脑泰方-成分-HT-CSVD-靶点”网络可视化关系图,并基于蛋白互作(PPI)网络分析数据库,确立脑泰方和HT-CSVD的PPI网络。最后,利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库对靶点进行富集分析;利用分子对接进行对接反向验证。结果脑泰方4味中药中有40种有效成分和804个预测靶点,393个潜在靶点可作用于HT-CSVD;脑泰方防治HT-CSVD的作用通路涉及细胞对氮化合物的反应、神经活性配体-受体互作等;在脑泰方药物的主要成分中,化合物西加小冠花苷(hyrcanoside)与表皮生长因子受体(EGFR)的结合度最高。结论本研究初步揭示了脑泰方防治HT-CSVD的主要活性成分、作用靶点和相关通路,为后续进一步探讨脑泰方靶向防治HT-CSVD提供了新思路。但本研究的分子机制探析存在一定的局限性,仍需细胞、动物、和分子层面的实验验证,从而为脑泰方防治HT-CSVD的临床和基础研究提供更为充分、完善的证据。Objective To explore the mechanisms of Naotaifang in the prevention and treatment of hypertensive cerebral small vessel disease(HT-CSVD)through the network pharmacology and molecular docking methods.Methods Firstly,the main effective components of Naotaifang were screened using The Traditional Chinese Medicine Database and Analysis Platform(TSMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)and TCM@Taiwan,and combined with related literature,and then their potential targets were predicted by PubChem database and Swiss Target Prediction database.Secondly,the targets related to hypertension and cerebral small vessel disease were screened by Genecards and Online Mendelian Inheritance in Man(OMIM)database respectively,and their intersection targets were used as the related targets of HT-CSVD.Again,Cytoscape 3.7.2 software was used to construct the"Naotaifang-ingredient-HT-CSVD-target"network visualization and establish the proteinprotein interactions between Naotaifang and HT-CSVD based on the protein interactions network analysis database.Finally,enrichment analysis of the targets was performed using Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)databases;docking reverse validation was performed using molecular docking.Results Naotaifang had 40 effective ingredients and 804 predicted targets in 4 herbs,and 393 potential targets could act on HT-CSVD;the pathways of action of Naotaifang against HT-CSVD involve cellular response to nitrogen compounds,neuroactive ligandreceptor interaction,etc.Among the main components of Naotaifang drug,the compound chyrcanoside had the highest binding to EGFR.Conclusion This study preliminarily speculated the main active ingredients,targets and related pathways of Naotaifang in the prevention and treatment of HT-CSVD,which provides a new idea for further study of the inhibition of HT-CSVD targeted by Naotaifang.However,there are limitations in the molecular mechanism of this study,and experimental validation at th

关 键 词：脑泰方 网络药理学 分子对接 高血压脑小血管病 作用机制 

分 类 号：R285[医药卫生—中药学]