目的 运用数据挖掘、网络药理学和分子对接的方法,探讨中药复方治疗中枢性性早熟（CPP）的用药规律和作用机制,为其临床治疗提供更多依据。方法 在中国知网（CNKI）、万方数据（Wanfang）、维普中文期刊（VIP）等数据库中检索从建库至2022年10月发表的中药复方治疗CPP的文献,用Excel 2021 收集整理临床治疗CPP的常用中药复方,并通过Excel 2021、SPSS Modeler 18.0、SPSS Statistics 25.0等软件对其进行频次、关联规律等分析,研究CPP治疗的用药规律。在上述基础上采用网络药理学的研究方法,筛选出高频药对的活性成分、作用靶点以及疾病的相关靶点,构建蛋白互作网络,并通过基因本体和京都基因 基因组百科全书通路富集分析来阐明药物的作用机制。最后运用 Autodock Vina 软件进行分子对接对结果验证。结果 共筛选出224篇文献,包含方剂133首,中药188味。发现18味使用超过25次的高频药物;清热类、补虚类的药物应用较多;药物性味以寒及苦为主;归经之中以肝经占比最高;进一步关联分析得到高频药对14个;核心处方4个。网络药理学结果显示,共得到44个活性成分、200个药物靶点、1 287个疾病靶点、70个共有靶点、573条GO富集条目及136条KEGG通路,药物主要成分槲皮素、山奈酚、β-谷甾醇作用于雌激素受体、黄体酮受体等核心靶点,通过内分泌抵抗、雌激素等信号通路发挥治疗作用。分子对接结果显示药物主要活性成分与相应核心靶点具有较好的结合能力。结论 中药复方治疗CPP多为滋阴清热、补虚类药物,与药性寒,药味苦、甘,归肝、肾经的药物配伍使用。其中高频药对“知母-黄柏”通过多成分、多靶点调控内分泌抵抗、雌激素信号通路发挥治疗作用。

Objective To explore the prescription rules and mechanism of traditional Chinese medicine（TCM） in the treatment of central precocious puberty（CPP）by using data mining,network pharmacology and molecular docking,so as to provide more evidence for clinical treatment．Methods Using the literature on the treatment of CPP with TCM compounds,which was retrieved from the databases of CNKI,Wanfang,VIP and other databases from the establishment of the database to October 2022 as the data sources．Excel 2021 was used to collect and summarize the commonly used TCM prescriptions for CPP,and conducted frequency analysis and association rules analysis of CPP by Excel 2021,SPSS Modeler 18.0,SPSS Statistics 25.0 and other software,so as to study the composition rule of prescriptions for CPP．On the basis of these results,network pharmacology method was used to screen out the active ingredients and action targets of high-frequency drugs,and then screen out the disease related targets to construct PPI network．Mechanism of drugs was clarified through GO and KEGG pathway enrichment analysis．Finally,the molecular docking of autodock Vina（Vina）platform was used to verify the results．Results A total of 244 documents met the search criteria,including 133 prescriptions and 188 traditional Chinese medicines．It had been found that 18 high-frequency Chinese medicines were used more than 25 times．The drugs mainly focused on clearing heat and supplementing deficiency．The medicinal flavors were mainly cold and bitter,which belonged to the liver channel．Further correlation analysis yielded 14 high-frequency drug pairs and 4 core prescriptions．The results of network pharmacological analysis showed that 44 active components,200 drug targets,1 287 disease corresponding targets,70 common targets,573 GO enrichment entries and 136 KEGG pathways targets were obtained．It has been found that the main components of the drugs,such as quercetin,kaempferol and β-sitosterol,act on the core targets of ESR1,PGR and play a therapeutic role through endocrine resistance and estrogen signaling pathways．Finally,molecular docking results showed that the main active ingredients of the drug had good binding ability with the corresponding core targets．Conclusions In the treatment of CPP,traditional Chinese medicine is mainly used types of nourish Yin,clear heat and replenish deficiency,which is compatible with the drugs with cold properties,bitter and pliant taste,and the liver and spleen channels．Among them,high-frequency drug pair “ZhiMu-HuangBai” play a therapeutic role in the regulation of endocrine resistance and estrogen signaling pathways through multi-components and multi-targets．

目的 探究中医药治疗盆腔炎的用药规律,为中医临床辩证用药提供借鉴。方法 采用主题词联合自由词相,全面检索CNKI、VIP、Wangfang、CBM、PubMed和EMbase、数据库及Cochrane图书馆,收集中、西药对比治疗盆腔炎的随机对照试验。严格按照纳入、排除标准挑选随机对照试验中涵盖的中药药方,采用Excel表格统计分析药方中药的四气、五味、归经和用药频率,随后利用系统聚类软件对使用频率高的中药开展关联、聚类和主成分分析。结果 本文共纳入235个随机对照试验,涉及320首中药处方,平均用药味数13.29味,使用频率前五位的药分别为延胡索、赤芍、当归、蒲公英、丹参;关联规则共得出41对高关联药对,其中包括赤芍-延胡索、莪术-三棱-败酱草等。高频率使用的前30味中药可分为五大类,获取的9个主成分分析结果与系统聚类中的结果一致。结论 本研究采用循证医学和系统聚类分析方法,剖析中医药治疗盆腔炎的用药规律,为临床用药提供参考。

Objective To discuss the medication regularity of traditional Chinese medicine (TCM) in the treatment of pelvic inflammatory disease, and provide new thinking for effective medication in clinical medicine. Methods Keywords combined with free word were used to comprehensively search CNKI, VIP, Wangfang, CBM, PubMed and EMbase, databases and Cochrane library to collect randomized controlled trials of comparative treatment of pelvic inflammatory disease between Chinese and Western drugs. The TCM prescriptions covered in the randomized controlled trial were selected in strict accordance with the standard inclusion and exclusion criteria. Excel was used to statistically analyze the four properties, five flavors, meridian and medication frequency of TCM prescriptions. Then, systematic clustering software was used to carry out correlation, clustering and principal component analysis for the Chinese medicines with high using frequency. Results The study included 235 randomized controlled trial and 320 prescriptions of traditional Chinese medicine were involved, the average number of herbs was 13.29, which Yanhusuo, Chishao, Danggui, Pugongying, Danshen were with top five frequency. A total of 41 drug pairs with high association were obtained by association rules, including Chishao-Yanhusuo, Eshu-Sanleng-Baijiangcao, etc. Thirty traditional Chinese medicine with high using frequency can be divided into 5 categories according to the effect. The obtained results of 9 principal component analysis were consistent with those in the system cluster. Conclusions In this study, evidence-based medicine and systematic cluster analysis were used to analyze the medication regularity of traditional Chinese medicine in the treatment of pelvic inflammatory disease, so as to provide reference for the clinical medication.