[关键词]
[摘要]
目的 利用网络药理学方法对黄芪进行多成分、多靶点研究,分析其在卒中相关性肌少症中的作用靶点及相关通路。方法 采用TCMSP数据库收集黄芪活性化合物并进行初步筛选;采用Swiss Target Prediction数据库预测活性化合物靶点,通过GeneCards数据库预测卒中相关性肌少症作用靶点,取两者交集获得交互靶点。采用String数据库及Cytoscape软件Network analyzer功能构建共同靶点PPI网络。采用DAVID数据库并结合Cytoscape软件对共同靶点进行GO及KEGG富集分析。结果 收集筛选出黄芪20个活性化合物,616个作用靶点,卒中相关性肌少症136个作用靶点,交集出25个交互靶点,其中AKT1、IL-6、TNF、IGF1R、ESR1等蛋白相互作用最明显,主要在细胞基质中影响类固醇结合、锌离子结合、蛋白质丝氨酸/苏氨酸激酶活性、雌激素受体活性、胰岛素及能量代谢等生物过程,通过胰岛素抵抗、HIF-1信号通路、TNF信号通路等在卒中相关性肌少症中发挥作用,AKT1、PI3CG、mTOR、IL-6、TNF等交互靶点在各通路中参与次数较多。结论 黄芪在卒中相关性肌少症中体现了多成分、多靶点、多途径的特点,其可能通过调控IRS-1/PI3K/AKT2/mTOR信号通路,靶向调控胰岛素抵抗途径相关能量代谢障碍,进而治疗和预防卒中相关性肌少症。
[Key word]
[Abstract]
Objective To study the multi-components and multi-targets of Astragali Radix membranaceus by using the method of network pharmacology, and to analyze the targets and related pathways of Astragali Radix in stroke-related myosis. Methods The active compounds of Astragali Radix were collected by TCMSP database and screened. Swiss Target Prediction database was used to predict the target of active compounds, and GeneCards database was used to predict the target of stroke-related myosis. The common target PPI network is constructed by using String database and Cytoscape software Network analyzer function. DAVID database and Cytoscape software were used to analyze the enrichment of GO and KEGG. Results Tatolly 20 active compounds of Astragali Radix, 616 targets, 136 targets of stroke-related myosis were selected, and 25 interactive targets were intersected, among which AKT1, IL-6, TNF, IGF1R, ESR1 and other proteins had the most obvious interaction. It is mainly in the biological processes of steroid binding, zinc ion binding, protein serine/threonine kinase activity, estrogen receptor activity, insulin and energy metabolism in cell matrix. Insulin resistance, HIF-1 signaling pathway, TNF signaling pathway and other pathways play a role in stroke-related myosis. Conclusion Astragali Radix embodies the characteristics of multi-component, multi-target and multi-pathway in strokerelated myosis. It may target the treatment and prevention of stroke-related myosis by regulating the role of IRS-1/PI3K/AKT2/mTOR signaling pathway in energy reward disorder under the influence of insulin resistance pathway.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金面上项目(81874463);湖南省科技厅科技创新平台与人才计划(2017SK4005);湖南中医药大学研究生创新课题项目(2018CX07);湖南中医药大学中西医结合一流学科开放基金项目(2018ZXYJH10)