中药复方治疗干燥综合征的配伍规律及作用机制研究

Compatibility and mechanism of a Chinese medicine compound in treating Sjogren’s syndrome

目的通过国家专利数据库,运用数据挖掘方法总结中药复方专利治疗干燥综合征(SS)的配伍特点及用药规律,根据网络药理学的分析方法,对高频药物治疗SS的潜在作用靶点及分子机制进行预测。方法登录“中国专利公布公告”网站检索并筛选建库至2022年12月10日治疗SS的中药复方专利数据。应用Microsoft Excel 2022、IBM SPSS Modeler 18.0等软件,对所纳入的专利复方进行频次统计、关联规则和聚类分析。利用中药系统药理学数据库(TCMSP)平台,获得中药化学成分及其潜在靶点并归纳分析;应用人类孟德尔遗传(OMIM)数据库、GeneCards等数据库对SS相关疾病靶点进行筛选,同时绘制韦恩图找到药物靶点与SS靶点的交集靶点,运用蛋白质相互作用数据库(STRING)构建蛋白质相互作用网络,并筛选出其最终的核心作用靶点;并登录Metascape网站寻找核心作用靶点富集的通路及其功能。结果根据对国家专利数据库的筛选结果,共得到69项符合条件的用于治疗SS的中药复方专利,其中包含353味药物,排名位于前5位的高频核心药物分别为麦冬、地黄、甘草、石斛、白芍;这5味药物共涉及161个化合物、1585个相关作用靶点,干燥综合征相关靶点1058个,中药与疾病共同靶点挖掘81个、核心靶点28个;通过富集分析得到京都基因与基因组百科全书(KEGG)通路177条,主要包括IL-17信号通路、PD-1/PD-L1通路,JAK-STAT信号通路等;基因本体(GO)生物工程(BP)3106条,主要涉及细胞对生物刺激因素、脂多糖反应、对细胞因子产生的正向调节的过程等;GO细胞组成(CC)193条主要涉及质膜外侧、膜微区等;GO分子功能(MF)289条主要涉及生长因子受体、受体配体活性等。结论中药复方专利治疗SS总以滋阴润燥,养阴生津为主。核心药物治疗SS具有多成分、核心靶点、多条通路相互协同特点,并且与IL-6、MMP3、SATA3、TNF等靶点关系密切,可能通过IL-17、PD-1/PD-L1通路等信号通路发挥作用,并为后续SS临床治疗提供新的用药参考及研究方向,也为中医药防治SS应用提供参考及分子生物学基础。

Objective To analyze the ways in which Chinese medicinal compound formulas are used in the treatment of Sjogren’s syndrome based on the National Patent Database and to predict the potential targets of action and molecular mechanisms of high frequency drugs in the treatment of Sjogren’s syndrome using analytical methods of network pharmacology.Methods Data on patent Chinese medicinal compound formulas for treating Sjogren’s syndrome was retrieved from the Chinese Patent Search Database as of December 10,2022.Microsoft Excel 2022 and IBM SPSS Modeler 18.0 were used to analyze these included compounds in terms of frequency,correlations and clustering analysis.The chemical components of TCM and their potential targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database(TCMSP)platform.OMIM and GeneCards were used to screen the Sjogren’Syndrome-related disease targets.The Venny diagram was drawn to identify the intersection targets of high-frequency drugs and Sjogren’s syndrome targets.The protein interaction network was constructed while the final core targets were screened by using the STRING database.The Metascape website was used to find the pathways and functions of high core target enrichment.Results According to the screening results via the national patent database,69 eligible Chinese medicine compound patents for the treatment of Sjogren’s syndrome were obtained,including 353 drugs,and the top 5 high-frequency drugs were Maidong(Dwarf Lilyturf Tuber),Dihuang(Rehmanniae Radix),Gancao(Licorice),Shihu(Dendrobium nobile Lindl)and Baishao(White Peony Root).These five drugs involved 161 compounds and 1585 related targets,1058 targets related to the Sjogren’s syndrome,81 treatment targets and 28 core targets.Through enrichment analysis,177 KEGG pathways were obtained,including IL-17 signaling pathway,PD-1/PD-L1 pathway and JAK-STAT signaling pathway.A total of 3106 GO biological processes(BPs)were retrieved,involving cellular responses to biological stimuli and lipopolysaccharides and the processes of positive regulation of cytokine production.The 193 GO cellular components(CCs)involved the outer plasma membrane and membrane microregions.Conclusion Sjogren’Syndrome is generally treated with Chinese medicinal compound formulas by nourishing Yin,moistening dryness and generating fluid.The medications for Sjogren’s Syndrome have multi-component,multi-target and multi-pathway properties and are closely related to IL-6,MMP3,SATA3 and TNF possibly through IL-17,PD-1/PD-L1 pathways.This study is expected to provide reference for subsequent clinical treatment of Sjogren’s syndrome.