基于文献挖掘和网络药理学探讨中药治疗卵巢早衰的作用机制
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摘要
卵巢早衰 (premature ovarian failure, POF) 病因复杂，治疗难度较大，现代研究显示中医药可以提高卵巢对促性腺激素的反应性和性激素受体含量，改善卵巢功能。本项目组结合文献挖掘和网络药理学分析，探索中医药治疗卵巢早衰的规律和潜在作用机制。从中国知网 (China National Knowledge Infrastructure, CNKI) 等数据库分别筛选近 30 年收录的相关临床研究文献，使用 NCINET 6.0 软件建立中药社群网络并进行中心性分析；利用中药系统药理学分析平台 (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP) 等数据库获取核心中药的关键成分和对应靶点；检索 OMIM 等基因数据库提取卵巢早衰疾病靶点，将核心药物靶点与卵巢早衰靶点取交集，构建活性成分-靶点网络和靶点蛋白-蛋白相互作用网络 (protein-protein, PPI network)；对交集基因进行基因本体 (gene ontology, GO) 富集分析和 KEGG (kyoto encyclopedia of genes and genomes) 通路富集分析，并对核心药物活性成分和靶点基因进行分子对接。共获得中药复方 135 个，中药 64 味；中心性较高的核心药物为 “仙茅-淫羊藿-当归-熟地”；4 味中药的有效化学成分有 81 个，核心药物组合与卵巢早衰的交集靶点 259 个，PPI 网络主要涉及 AKT1、JUN、IL6、EGFR、MAPK1、RELA 等关键靶蛋白，GO 功能富集分析，得到生物过程条目 2,139 个 (p＜0.05)，KEGG 富集得到 181 条通路 (p＜0.05)，主要涉及糖基化终末产物 (AGE)/糖基化终末产物受体 (RAGE) 信号通路、化学致癌–受体激活通路、肿瘤坏死因子受体 (tumor necrosis factor, TNF) 介导的信号通路、白细胞介素-17 (interleukin-17, IL-17) 信号通路等。分子对接结果显示四味中药主要成分与治疗卵巢早衰的关键靶点结合活性较高且对接构象较稳定。中药中的关键活性成分阿魏酸等可通过调控 AKT1、JUN、IL6 等关键靶点，借助 AGE-RAGE 信号通路、化学致癌–受体激活通路、TNF 信号通路、IL-17 信号通路等等发挥抗卵巢早衰的作用。
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