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基于网络药理学的菟丝子-枸杞子药对治疗卵巢早衰的作用机制

研究 Δ

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李锦英 ，张兆萍 ，叶金飞 ，曾丽华 ，梁蕴仪 ，朱 玲 （1.广州中医药大学第一临床医学院，广州 510405；
2.广州中医药大学第一附属医院妇科，广州 510405）
中图分类号 R285；R711.75 文献标志码 A 文章编号 1001-0408（2020）18-2202-08
DOI 10.6039/j.issn.1001-0408.2020.18.05
摘 要 目的：探讨菟丝子-枸杞子药对治疗卵巢早衰的潜在作用机制。方法：利用中药系统药理学数据库与分析平台（TCMSP）、
GenenCards和OMIM数据库获得菟丝子-枸杞子药对活性成分及卵巢早衰的相关靶点，利用Venn在线工具筛选两者的交集基因，
并采用Cytoscape 3.7.0软件构建活性成分-靶点网络和靶点间蛋白-蛋白相互作用（PPI）网络；通过DAVID数据库对交集基因进行
基因本体（GO）富集分析和KEGG通路富集分析，最终构建活性成分-靶点-关键通路网络。结果：筛选出菟丝子-枸杞子药对活性
成分42个，成分及疾病靶点231、1 913个，节点度值排名靠前的化合物有槲皮素、山柰酚、β-谷甾醇、异鼠李素、黄豆黄素、豆甾醇和
芝麻素等。活性成分靶点与卵巢早衰疾病靶点的交集基因共149个，交集基因的PPI网络共包含节点149个、边2 970条，平均节
点度值为39.9，平均介数值为0.005 4。GO分析结果显示，上述交集基因的分子功能主要包括蛋白结合、酶结合等，生物过程主要
涉及促进RNA聚合酶Ⅱ启动子转录、促进DNA转录等，细胞组分主要包括细胞核、细胞质等，信号通路主要涉及癌症信号通路、
乙型肝炎通路、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路等。活性成分-靶点-
关键通路网络显示，菟丝子和枸杞子的主要活性成分均为黄酮类及醇类，关键靶点有蛋白激酶 B1（AKT1）、肿瘤抑制蛋白 P53
（TP53）、白细胞介素 6（IL6）、肿瘤坏死因子（TNF）等，通路主要涉及癌症信号通路、乙型肝炎信号通路、PI3K/AKT 信号通路、
MAPK信号通路等。结论：菟丝子-枸杞子药对的多种活性成分可能通过PI3K/AKT信号通路、MAPK等多条通路作用于AKT1、
TP53等多个靶点治疗卵巢早衰，并挖掘出潜在活性成分豆甾醇、芝麻素以及潜在靶点IL6、TNF。
关键词 菟丝子-枸杞子药对；卵巢早衰；网络药理学；作用机制

Study on the Mechanism of Couplet Medicine of Cuscutae Semen-Lycii Fructus in the Treatment of
Premature Ovarian Failure Based on Network Pharmacology
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LI Jinying ，ZHANG Zhaoping ，YE Jinfei ，ZENG Lihua ，LIANG Yunyi ，ZHU Ling（1. The First Clinical
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College，Guangzhou University of TCM，Guangzhou 510405，China；2. Dept. of Gynecology，the First
Affiliated Hospital of Guangzhou University of TCM，Guangzhou 510405，China）
ABSTRACT OBJECTIVE：To investigate the potential mechanism of couplet medicine of Cuscutae Semen-Lycii Fructus in the
treatment of premature ovarian failure. METHODS：Main active components and related targets of couplet medicine of Cuscutae
Semen-Lycii Fructus in the treatment of premature ovarian failure were obtained from TCMSP，GeneCards and OMIM database.
The intersection genes between them were screened using Venn online tool. Cytoscape 3.7.0 software was adopted to establish the
active ingredients-target network and the PPI network. GO and KEGG pathway enrichment analysis on intersection genes were
carried out by DAVID database. Finally，an active component-target-key pathway network was constructed. RESULTS：Totally 42
active components，231 and 1 913 targets for active components and disease were obtained from couplet medicine of Cuscutae
Semen-Lycii Fructus. The components with high node degree included quercetin，kaempferol，β-sitosterol，isorhamnetin，glycitein，
stigmasterol and sesamin，etc. There were 149 intersection genes between the active component targets and premature ovarian
failure targets. PPI network contained 149 nodes and 2 970 edges，with an average node degree of 39.9 and an average medium of
0.005 4. The results of GO analysis showed that molecule function of the above-mentioned genes mainly involved protein binding，
enzyme binding，etc. Biological process mainly included that positive regulation of transcription from RNA polymerase Ⅱ
promoter，positive regulation of transcription DNA-templated，
Δ 基金项目：国家自然科学基金资助项目（No.81674016）；国家中 etc. Cell components mainly included nucleus，cytoplasm，etc.
医药管理局全国中医学术流派传承工作室“岭南罗氏妇科流派传承工
Signaling pathway mainly involved cancer signaling pathway，
作室”建设项目（No.国中医药人教函〔2019〕62号）；广东省名中医传承
hepatitis B signling pathway，PI3K/AKT signaling pathway，
工作室建设项目（No.粤中医办函〔2019〕5号）
MAPK signaling pathway， etc. The results of active
＊硕士研究生。研究方向：中医药防治妇科疾病。E-mail：
617693370@qq.com component-target-key pathway network showed that active
# 通信作者：主任中医师，博士生导师，博士。研究方向：卵巢功 components of Cuscutae Semen and Lycii Fructus were
能障碍的中医药基础与临床。E-mail：2275898821@qq.com flavonoids and alcohols；key target included AKT1，TP53，

·2202 · China Pharmacy 2020 Vol. 31 No. 18 中国药房 2020年第31卷第18期