基于整合药理学的安子调冲方改善复发性流产合并抗磷脂综合征的分子机制研究  

Investigation of Molecular Mechanism of Anzi Tiaochong Fang in Improving Recurrent Spon⁃taneous Abortion with Antiphospholipid Syndrome Base on Integrated Pharmacology

作　　者：何珊 宁艳 马飞 蒋绍艳[1] 刘大艳[1] 王智玮 吴芳婷 HE Shan;NING Yan;MA Fei;JIANG Shaoyan;LIU Dayan;WAGN Zhiwei;WU Fangting(The Affiliated Shenzhen Maternity and Child Healthcare Hospital,Southern Medical University,Shenzhen,Guangdong 518028,China)

机构地区：[1]南方医科大学附属深圳市妇幼保健院,广东深圳518028

出　　处：《福建中医药》2022年第5期10-14,30,共6页Fujian Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82104576);广东省基础与应用基础研究基金项目(2019A1515110579);广东省中医药局科研项目(20201292);深圳市“医疗卫生三名工程”项目—广州中医药大学第一附属医院罗颂平教授中医药妇产科团队(SZSM201612046);深圳市科技创新委员会面上项目(JCYJ20210324130012031,JCYJ20210324130013033)。

摘　　要：目的探究安子调冲方(ATF)治疗复发性流产合并抗磷脂综合征(RSA/APS)的分子作用机制。方法在中医药整合药理学研究平台V2.0(TCMIPV2.0)收集ATF组方的化学成分及作用靶标,同时收集RSA/APS疾病靶标,应用GeneCards数据库、在线人类孟德尔遗传(OMIM)数据库完善RSA/APS靶标,预测ATF治疗RSA/APS的潜在靶标;在STRING平台对潜在靶标进行蛋白互作网络(PPI)的构建;对潜在靶标进行生物过程(GO)分析和通路富集(KEGG)分析,构建“中药复方-成分-潜在靶标-关键功能及通路”的网络,对网络中核心化学成分进行ADMET水平分析。结果共收集到ATF中的化学成分256种、靶标847个和疾病靶标500个,ATF和RSA/APS靶标进行互作关系分析获得潜在靶标45个。靶标主要富集于核因子-κB(NF-κB)进入细胞核的正调节、炎症应答、生成白介素-6(IL-6)的正调节和趋化因子产生的正调控等功能;主要富集于NF-κB信号通路和Toll样受体信号通路等通路。结论ATF中化学成分可能通过NF-κB进入细胞核的正调节、炎症应答、IL-6的正调节及Toll样受体信号通路等功能和通路以改善RSA/APS。Objective:To explore the potential molecular mechanism of Anzi Tiaochong Fang(ATF)in treating recurrent spontaneous abortion with antiphospholipid Syndrome(RSA/APS).Methods:The chemical constituents and drug targets of ATF were collected by Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP V2.0).RSA/APS disease target information was collected by TCMIP V2.0 and improved by Online Mendelian Inheritance in Man(OMIM)database and GeneCards database.The potential targets of ATF for RSA/APS were predicted,and the protein-protein interaction(PPI)network was constructed.Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for potential targets.Finally,the multidimensional network of traditional Chinese medicine compound-constituents-potential targets-core pathways was constructed.The levels of absorption,distribution,metabolism,excretion and toxicity(ADMET)of the main constituents in the network were analyzed.Results:A total of 256 chemical constituents and 847 targets were collected from ATF.A total of 500 targets of RSA/APS were obtained.A total of 45 potential targets were obtained by the interrelationship analysis of drug and disease targets.These targets might participate in treating RSA/APS by affecting biological processes,such as positive regulation of NF-kappaB(NF-κB)import into nucleus,inflammatory response,positive regulation of interleukin-6 production,positive regulation of chemokine production and so on.Pathway analysis showed that these targets were mainly enriched in NF-κB signaling pathway and Toll-like receptor signaling pathway.Conclusion:The main constituents of ATF were likely to treat RSA/APS by positive regulation of NF-κB import into nucleus,inflammatory response,positive regulation of interleukin-6 production,Toll-like receptor signaling pathway and so on.

关 键 词：安子调冲方 整合药理学 复发性流产 抗磷脂综合征 靶标 核心成分 网络 分子机制 

分 类 号：R285.5[医药卫生—中药学]