基于网络药理学方法探究银杏二萜内酯葡胺注射液治疗脑梗死的药理学机制  

Pharmacological Mechanism of Ginkgo Diterpene Lactone Glucosamine Injection in the Treatment of Cerebral Infarction Based on Network Pharmacology

作　　者：赵晨阳 郭利平[2] ZHAO Chenyang;GUO Liping(Zhejiang Chinese Medical University,Hangzhou 310053,China;Tianjin University of Traditional Chinese Medicine)

机构地区：[1]浙江中医药大学,浙江杭州310053 [2]天津中医药大学

出　　处：《西部中医药》2022年第8期73-79,共7页Western Journal of Traditional Chinese Medicine

基　　金：天津市教委基金(15ZXLCSY00020)。

摘　　要：目的:基于网络药理学方法研究银杏二萜内酯葡胺注射液治疗缺血性脑卒中的作用机制。方法:从PubChem下载银杏二萜内酯葡胺注射液的有效成分银杏内酯A、B、K的3D结构,在PharmMapper上传,获取预测的靶点,按可能性打分。将银杏内酯A、B、K的相关靶点对应的基因名称输入STRING数据库,得到蛋白互作(PPI)网络。将基因和化合物信息输入Cytoscape 3.7.1,绘制化合物-靶点药物调控网络。最后使用R语言软件计算,得到基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。以P<0.05为差异有统计学意义。结果:3个化合物预测靶点共217个,核心靶标主要有FGF1、UNC45A、USP19、HDAC6、CDKN1B、KPNB1、HSP90AB1、DDX58、PAX6、SNX9、CUL5、CACYBP、RNF8、TRAF4、SIRT3、HDAC7、EZR、MARK1等,可能通过代谢途径、黏附连接、紧密连接、内质网中的蛋白质加工、病毒感染及Rap1、MAPK、PI3K-Akt、Wnt、IL-17、AGE-RAGE等信号通路,影响热休克蛋白结合、泛素(样)蛋白连接酶结合、组蛋白脱乙酰酶活性、组蛋白乙酰转移酶结合、S100蛋白结合、tau蛋白结合等功能,从而参与缺血性脑卒中的一系列生理病理过程。结论:通过网络药理学可以预测银杏二萜内酯葡胺注射液的核心基因靶点、功能及相关信号通路,体现出其多成分、多靶点、多途径的生物学效应。Objective:To study the mechanism of ginkgo diterpene lactone glucosamine injection in treating cerebral infarction based on network pharmacology.Methods:Three dimensional structures of ginkgolides A,B and K,the main active ingredients of ginkgo diterpene lactone glucosamine injection were downloaded from PubChem,uploaded into PharmMapper to obtain the predicted targets and scored according to the possibility.The corresponding genetic names of ginkgolides A,B and K were typed into string database to obtain PPI internet.The information and gene and chemical compound were entered into Cytoscape3.7.1,to draw compound-target drug regulatory network.By calculated with R language software consequently,functional enrichment analysis of GO and KEGG pathway enrichment analysis were gained.And The difference was statistically significant(P<0.05).Results:All 217 prediction targets were involved from three compounds,and the core targets mainly were FGF1,UNC45A,USP19,HDAC6,CDKN1B,KPNB1,HSP90AB1,DDX58,PAX6,SNX9,CUL5,CACYBP,RNF8,TRAF4,SIRT3,HDAC7,EZR and MARK1.The participation in a series of physiological and pathological processes of ischemic stroke might be affected by heat shock protein binding,ubiquitin(like)protein ligase binding,histone deacetylase activity,histone acetyl transferase binding,S100 protein binding and tau protein binding,which might be through such signaling pathways as metabolic pathway,adhesion connection,tight connection,protein processing in endoplasmic reticulum,viral infection,Rap1,MAPK,PI3K-Akt,Wnt,IL-17 and AGERAGE.Conclusion:Core gene targets,the function and the relevant signaling pathway of ginkgo diterpene lactone glucosamine injection are predicted by network pharmacology,and it reflects the biological effects of multiple components,multiple targets and multiple pathways.

关 键 词：网络药理学 银杏二萜内酯葡胺注射液 脑卒中 

分 类 号：R255.2[医药卫生—中医内科学]