裘氏妇科治疗先兆流产的共性规律及常用药对分子机制的研究  

Research on Common Law of Treating Threatened Abortion Treatment of QIU's Gynecology and Molecular Mechanism of Common Drug Pair

作　　者：陈星蓓 张浩龙 王玲[2] 杨华娣[1] 王洁[1] 王佳曦[1] 陈文俊[1] CHEN Xingbei;ZHANG Haolong;WANG Ling;YANG Huadi;WANG Jie;WANG Jiaxi;CHEN Wenjun(The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,Zhejiang,China;Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,Zhejiang,China;Advanced Medical and Dental Institute,University Sains Malaysia,Pulau Penang Malaysia,Bertam 13200,Kepala Batas)

机构地区：[1]浙江中医药大学附属第一医院(浙江省中医院),浙江杭州310006 [2]浙江中医药大学附属杭州市中医院,浙江杭州310007 [3]Advanced Medical And Dental Institute,University Sains Malaysia,Pulau Penang Malaysia,Bertam 13200 Kepala Batas

出　　处：《中华中医药学刊》2023年第12期240-246,I0042-I0046,共12页Chinese Archives of Traditional Chinese Medicine

基　　金：浙江省科学技术厅重点研发计划项目(2021C03080);浙江省基础公益研究计划项目(LGF22H270006);浙江省中医药科技计划项目(2022ZB127);浙江中医药大学大学生创新创业训练计划项目(S202010344052)。

摘　　要：目的基于数据挖掘、网络药理学和分子对接分析浙江省裘氏妇科流派治疗先兆流产的中医思辨特征、共性规律,并探讨常用药对的可能作用机制。方法收集省内具有一定影响力的4位裘氏妇科传承人治疗先兆流产的病例,利用SPSS 22.0和Apriori关联规则算法筛选治疗先兆流产的高频药物及药对。应用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选药用药对的活性成分、潜在靶点,并与先兆流产相关靶点作比对,构建“核心靶点-活性成分-药物”网络。运用STRING数据库得到蛋白-蛋白相互作用(protein-protein interaction,PPI)网络。通过Metascape进行基因本体(gene ontology,GO)与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。使用分子对接和分子动力学对药物关键成分、核心靶点进行验证。结果先兆流产临床常见证型包括肾虚证、血热证、气血虚弱证、血瘀证,针对不同证型,4位医家辨证论治,异中存同,其中菟丝子-白芍是最常用药对。通过TCMSP数据库共筛选出该药对的22种活性成分及125个治疗先兆流产的靶点。GO功能富集分析主要集中于对含氮化合物的反应、脂多糖分子的免疫反应、激酶调节活性等过程。KEGG分析显示主要富集于参与癌症通路和P53信号通路等相关信号通路。分子对接结果显示菟丝子-白芍药对的活性成分槲皮素(quercetin)和山柰酚(kaempferol)能较好地与AKT1、TNF、IL6、TP53、VEGFA、IL1B、JUN、CASP3、EGF和MMP9等靶基因结合,具有潜在较高的生物活性。通过50 ns的分子动力学模拟发现菟丝子-白芍对形成了稳定的分子间作用。结论裘氏妇科治疗先兆流产组方用药多从脾、肾、肝论治,且善用药对,其常用药对“菟丝子-白芍”治疗先兆流产的潜在靶点和作用机制主要参与调控生殖激素�Objective Based on data mining,network pharmacology and molecular docking analysis,this study aims to explore the distinctive characteristics and common patterns of the QIU's Gynecology in the treatment of threatened miscarriage and investi⁃gate the potential mechanisms of commonly used herbal medicine pairs.Methods It collected case studies of threatened miscar⁃riage treated by four influential practitioners of the QIU's Gynecology in Zhejiang Province.SPSS 22.0 and the Apriori association rule algorithm were used to identify high-frequency drugs and drug pairs for the treatment of threatened miscarriage.The Tradi⁃tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was utilized to screen the active ingre⁃dients and potential targets of the selected herbal medicine pairs,which were then compared with the targets related to threatened miscarriage to construct a“core target-active ingredient-drug”network.The protein-protein interaction(PPI)network was constructed using the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrich⁃ment analyses were performed using Metascape.Molecular docking and molecular dynamics simulations were employed to validate the key components of the drugs and the core targets.Results The common clinical patterns of threatened miscarriage included kidney deficiency,blood heat,Qi and blood deficiency,and blood stasis.The four physicians employed different TCM syndrome differentiation and treatment methods,but shared commonalities.The most commonly used drug pair was Tusizi(Cuscutae Se⁃men)and Baishao(Paeoniae Radix Alba).Through the TCMSP database,22 active ingredients and 125 target proteins for the drug pair were identified.GO enrichment analysis showed involvement in nitrogen compound response,lipopolysaccharide im⁃mune response and kinase regulator activation.KEGG analysis revealed enrichment in cancer-related pathways and the P53 sig⁃naling pathway.Molecular docking results demonstrated that the active co

关 键 词：先兆流产 裘笑梅 浙派裘氏妇科 共性规律 数据挖掘 网络药理学 分子对接 分子动力学 

分 类 号：R271.1[医药卫生—中医妇科学]