目的:基于数据挖掘和网络药理学分析金明秀教授治疗干燥综合征的用药规律及机制.方法:收集金明秀教授于2021年3月-2023年3月治疗干燥综合征的医案,建立数据库,运用EXCEL、SPSS Modeler 18.0等软件进行数据挖掘,挖掘出核心处方中的高频药物,对高频药物进行关联分析、聚类分析,得到有效方.通过BATMAN-TCM及ETCM数据库检索核心药物组合的活性成分,检索本草组鉴中核心药物的相关靶点.通过对GeneCards和DisGeNET数据库检索去重得到疾病靶点,运用Venny平台得到疾病与药物的交集靶点;运用CytoScape 3.9.0建立药物-靶点网络图;应用STRING数据库对得到的交集靶点绘制蛋白质-蛋白质相互作用网络图,筛选核心靶点;通过DAVID数据库对交集靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析.结果:涉及处方312首,药物147味,使用频率最高的20味药物有白芍、茯苓、泽泻等.高频药物以寒性、苦味,归肝经、肺经、胃经为主.高频药物聚类分析分为五大类.对核心药物进行网络药理分析,获得核心药物靶点2 437个,干燥综合征疾病相关靶点843个,其中核心药物及干燥综合征共同靶点148个.通过对这些靶点进行GO生物过程及KEGG信号通路的富集分析,初步预测出核心药物可能是通过白桦脂醇、马兜铃酮、葫芦巴碱、麻黄碱、八仙花酸等有效成分,调节雌激素受体1(Estrogen Receptor 1,ESR1)、雄激素受体(Androgen Receptor,AR)、核受体亚家族3组C成员1(Nuclear Receptor Subfamily 3 Group C Member 1,NR3C1)、蛋白激酶 Cα(Protein Kinase C Alpha,PRKCA)、前列腺素氧化环化酶 2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、白细胞介素-1β(Interleukin-1β,IL-1β)、B 淋巴细胞瘤-2 相关 X 蛋白(B lymphoblastoma-2-associated X Protein,BAX)、溶质载体家族6成员 4(Solute Carrier Family 6 Member 4,SLC6A4)、甾醇-O-酰基转移酶 1(Sterol O-acyltransferase 1,SO AT1)、转化生长因子 β1(Transforming Growth Factor Beta 1,TGFβ1)等靶点,调控细胞凋亡、核因子-κB(Nuclear Factor-κB,NF-κB)信号通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、磷脂酰肌醇 3 激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶 B(Akt)信号通路、酪氨酸蛋白激酶(Janus-activated Kinase,JAK)-STAT信号通路等.结论:金明秀教授治疗干燥综合征多用清热燥湿解毒、活血化瘀、健脾化湿、滋阴润燥的药物,核心药物组合通过多靶点、多通路治疗该疾病,为临床治疗开拓了新思路.
JIN Mingxiu's experience in treating Sjogren's syndrome based on data mining and network pharmacology
Objective:Based on data mining and network pharmacology,the medication rule and action mechanism of treating Sjogren's syndrome by JIN Mingxiu was analyzed.Methods:Professor JIN Mingxiu's medical records about the treatment of Sjogren's syndrome from March 2021 to March 2023 were collected to establish a database.Data mining was performed by Excel,SPSS Modeler 18.0 and so on.The high-frequency drugs in the core prescriptions were mined out,and the effective prescriptions were obtained by association analysis and cluster analysis.BATMAN-TCM and ETCM databases were used to retrieve the active components of the core drug combinations,and the related targets of the core drugs were retrieved by HERB database.The disease targets were obtained by searching GeneCards and DisGeNET database and removing duplicate data.The intersection target of disease and drug was obtained by Venny platform.CytoScape 3.9.0 was used to establish a drug-target network.The PPI network graph of intersection targets was drawn by STRING database to screen the core targets.The GO analysis and KEGG enrichment analysis were performed on the intersecting targets using the David Database.Results:A total of 312 prescriptions were involved,with 147 drugs,the 20 most frequently used drugs were Baishao(Radix Paeoniae Alba),Fuling(Poria),Zexie(Rhizoma Alismatis),etc..The high-frequency drugs were mainly cold and bitter,and mainly were absorbed by liver,lung and stomach meridians.The cluster analysis of high-frequency drugs showed there were five categories.Through network pharmacological analysis,2 437 core drug targets and 843 Sjogren's syndrome disease-related targets were obtained,of which 148 were common targets of core drugs and Sjogren's syndrome.Through the enrichment analysis of GO biological process and KEGG signal pathway,it is preliminarly predicted that the core drug may be act on ESR1,AR,NR3C1,PRKCA,PTGS2,IL-1β,BAX,SLC6A4,SOATl,TGF-β1 and other targets to regulate apoptosis,NF-κB signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and JAK-STAT signaling pathway by betulin,aristolochinone,trigonelline,ephedrine,hydrangeic acid and other active ingredients.Conclusion:Professor JIN Mingxiu mainly uses the drugs for clearing away heat and dampness and detoxifying,promoting blood circulation and removing blood stasis,invigorating spleen and removing dampness,and nourishing Yin(阴)and moistening dryness in the treatment of Sjogren's syndrome.The core drug combination treats the Sjogren's syndrome through multiple targets and pathways,which provides new ideas for its clinical treatment.
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