基于网络药理学的加味佛手散抑制子宫内膜侵袭转移机制研究  

Mechanism of Jiawei Foshou San on invasion and metastasis in endometriosis based on network pharmacology

作　　者：张莹 韦佳慧 张成玲 李攀红[1] 孙文威 徐晓玉[1] 陈怡[1] ZHANG Ying;WEI Jia-hui;ZHANG Cheng-ling;LI Pan-hong;SUN Wen-wei;XU Xiao-yu;CHEN Yi(College of Pharmaceutical Sciences and Chinese Medicine,Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine,Pharmacology of Chinese Materia Medica-the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine,Southwest University,Chongqing 400715,China)

机构地区：[1]西南大学药学院&中医药学院,重庆市高校中药新药筛选重点实验室,国家中医药管理局中药药理重点建设学科,重庆400715

出　　处：《药学学报》2018年第9期1398-1405,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81773984,81402441); 重庆市卫生局中医药科研项目(zy201602125); 西南大学“国家级大学生创新创业训练计划”项目(201710635073)

摘　　要：加味佛手散是由川芎嗪、阿魏酸加延胡索乙素组成的新中药复方。前期研究发现,加味佛手散能够抑制异位子宫内膜生长,但对异位内膜侵袭转移的作用尚不明确。本研究运用网络药理学方法分析加味佛手散作用靶点,并通过体内模型验证其对异位内膜侵袭转移的作用机制。首先,通过检索TCMID、TCMSP和SEA数据库获得加味佛手散成分靶点,检索OMIM、Dis Ge NET和GEO数据库获得子宫内膜异位症的靶点,采用Cytoscape3.5.0软件构建加味佛手散成分-成分靶点和加味佛手散成分-子宫内膜异位症靶点网络,并将关键靶点的信息上传至DAVID数据库进行通路富集分析,发现加味佛手散可能通过调控MMP2、MMP9、TIMP1、ICAM1和VEGFA等66个关键靶点,干预雌激素、HIF-1、TNF和Gn RH信号通路等115条通路发挥作用,其中MMP-TIMP为一类关键靶点。其次,加味佛手散体内能显著抑制异位内膜组织的生长,下调MMP-2和MMP-9,上调TIMP-1表达,进而抑制异位内膜侵袭转移。此结果为加味佛手散的研究提供了药效学依据。Jiawei Foshou San is a new Chinese medicine compound consisting of ligustrazine, ferulic acid and fumarate. Previously Jiawei Foshou San inhibited the growth of endometriosis with unclear mechanism, especially in metastasis and invasion. In this study, network pharmacology analysis was performed to explore potential mechanism of Jiawei Foshou San on endometriosis. Jiawei Foshou San compound targets were purchase from TCMID, TCMSP and SEA database. Endometriosis targets were collected from OMIM, Dis Ge NET and GEO database. Networks of Jiawei Foshou San compound-compound targets and compound target-endometriosis target were established with Cytoscape 3.5.0 software. Key targets were analyzed for pathway enrichment through DAVID database. It was found that Jiawei Foshou San regulated 66 core targets（MMP2, MMP9, TIMP1, ICAM1, VEGFA, et al.） and affected 115 pathways, such as estrogen, HIF-1, TNF and Gn RH signaling pathways. MMP-TIMP were uncovered as one cluster of the core targets. Furthermore, Jiawei Foshou San significantly suppressed the growth of ectopic endometrium. Meanwhile, invasion and metastasis were restrained after treating with Jiawei Foshou San through decreasing MMP-2 and MMP-9, increasing TIMP-1. In brief, these results provide a pharmacodynamic basis for the study of Jiawei Foshou San.

关 键 词：加味佛手散 子宫内膜异位症 网络药理学 侵袭转移 作用机制 

分 类 号：R966[医药卫生—药理学]