基于网络药理学的桂枝加葛根汤治疗颈椎病作用机制研究  

Study on the Mechanism of Guizhi with Gegen Decoction in Treatment of Cervical Spondylosis Based on Network Pharmacology

作　　者：董永丽[1] 白子兴 高云 魏戌[1] 张兴平[1] 杨丽平[1] DONG Yong-li;BAI Zi-xing;GAO Yun;WEI Xu;ZHANG Xing-ping;YANG Li-ping(Wangjing Hospital of China Academy of Chinese MedicalSciences,Beijing 100102;Eye Hospital of China Academy of Traditional Chinese Medicine Sciences,Beijing 100040)

机构地区：[1]中国中医科学院望京医院,北京101002 [2]中国中医科学院眼科医院,北京100040

出　　处：《世界中西医结合杂志》2020年第7期1215-1219,1226,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：国家中医药管理局基地专项(JDZX2015277);北京市科学技术委员会科技新星项目(Z191100001119025)。

摘　　要：目的查询筛选桂枝加葛根汤治疗颈椎病的靶点、通路,明确桂枝加葛根汤的药理学作用。方法通过TCMSP中药系统药理学数据库与分析平台,定义生物利用度(OB)≥30%,类药性(DL)≥0.18,获得桂枝加葛根汤的有效成分,利用UniProt系统确定靶点基因,然后查询OMIM、DisGeNET、GeneCards等数据库,挖掘颈椎病相关的基因靶点。最后对两种靶点基因取交集,运用STRING数据库和Cytoscape软件,构建中药-成分-靶基因-疾病的中药调控网络,查找桂枝加葛根汤治疗颈椎病的核心靶点基因,对核心蛋白进行GO和KEGG的分析。结果桂枝加葛根汤的有效化学成分共1001个,筛选后获得最终150个,基因靶点221个。确定颈椎病靶点12171个,二者共同靶点基因180个,PPI网络分析发现STAT3、AKT1、JUN、IL6、MAPK、EGFR可能是桂枝加葛根汤治疗颈椎病的关键靶点。GO富集分析确定了154个条目(P<0.05),其中生物过程主要包括DNA结合转录激活剂活性、酰胺结合、细胞因子受体结合等;KEGG通路富集分析明确了166条信号通路,其中信号通路涉及肿瘤相关通路、肝炎相关通路、炎症相关通路以及细胞再生与修复等通路。结论桂枝加葛根汤通过多靶点、多通路作用于颈椎病,主要起到抗炎免疫的作用,后期需要借助分子对接与生物实验验证靶点的有效性,明确桂枝加葛根汤的作用机制,为临床用药组方提供新思路。Objective Tofind the target and pathway of GuizhiwithGegenDecoction for the treatment of cervical spondylosis,and clarify the pharmacological effects of GuizhiwithGegen Decoction.Methods Based on the TCMSP Chinese medicine system pharmacology database and analysis platform,the bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 were defined.The active ingredients of GuizhiwithGegenDecoction were obtained,and the target gene was determined using the UniProt system.Query databases such as OMIM,DisGeNET,GeneCards,etc.,to determine the gene targets related to cervical spondylosis.Finally,the two target genes are intersected,and the STRING database and Cytoscape software are used to build a traditional Chinese medicine regulatory network of Chinese medicine-components-target genes-disease,and find the core target genes of GuizhiwithGegenDecoction for the treatment of cervical spondylosis.Core proteins were analyzed for GO and KEGG.Results There were 1001 effective chemical constituents of GuizhiwithGegen Decoction.After screening,150 final genes and 221 gene targets were obtained.12171 cervical spondylosis targets were identified,and 180 common target genes were detected by PPI network analysis.It was found that STAT3,AKT1,JUN,IL6,MAPK,and EGFR may be the key targets for GuizhiwithGegen Decoction to treat cervical spondylosis.GO enrichment analysis identified 154 entries(P<0.05),of which biological processes mainly include DNA binding transcription activator activity,amide binding,cytokine receptor binding,etc;KEGG pathway enrichment analysis identified 166 signal pathways,of which Signaling pathways involve tumor-related pathways,hepatitis-related pathways,inflammation-related pathways,and cell regeneration and repair pathways.Conclusion GuizhiwithGegenDecoction acts on cervical spondylosis through multiple targets and multiple pathways,and it mainly plays an anti-inflammatory and immunological role.In the later stage,molecular docking and biological experiments are needed to verify the effectiveness of the target

关 键 词：桂枝加葛根汤 颈椎病 网络药理学 作用机制 

分 类 号：R681.55[医药卫生—骨科学]