目的 总结国医大师周仲瑛治疗乳腺增生的用药规律，预测核心中药组合治疗乳腺增生的潜在作用机制。方法 整理周仲瑛教授诊治乳腺增生的门诊电子病历，对纳入中药的使用频次、性味归经进行统计，并对其进行关联规则分析和系统聚类分析，总结用药规律及挖掘核心中药组合。利用网络药理学和分子对接技术探究核心中药组合治疗乳腺增生的潜在作用机制。结果 共纳入 145 例患者、386 首处方和 270 味中药。频次统计分析发现周仲瑛教授治疗乳腺增生用药性味以寒、苦为主，归经以肝经为主；关联规则和系统聚类分析获得核心中药组合为香附-柴胡-夏枯草。用网络药理学方法获得核心中药组合的活性成分 37 个，治疗乳腺增生的潜在作用靶点 122 个。通过蛋白质-蛋白质相互作用网络 （PPI） 分析确定了 10 个核心靶点，包括信号转导及转录激活因子 3 （STAT3）、磷酸肌醇 3-激酶调节亚基 1 （PIK3R1）、雌激素受体 1 （ESR1） 等。京都基因与基因组百科全书 （KEGG） 通路分析发现，核心中药组合的活性成分主要通过 PI3K-Akt、Ras、EGFR 等信号通路作用于乳腺增生，并与癌症中的中心碳代谢和蛋白聚糖等途径密切相关。分子对接结果显示，ESR1、SRC、AKT1 与 β-谷甾醇，ESR1 与木犀草素具有良好的结合能力及稳定性。结论 周仲瑛教授辨治乳腺增生时抓住“肝郁”的本质，治法以调理肝气，疏通乳络为主，兼以清火、化痰、行瘀。核心中药组合香附-柴胡-夏枯草的主要成分以木犀草素、β-谷甾醇为代表，作用于 AKT1、ESR1 等靶点，通过 PI3K-Akt、Ras、EGFR 以及癌症相关信号通路等途径发挥治疗乳腺增生的作用。

Objective To summarize the medication rule of traditional Chinese medicine （TCM） master Zhou Zhongying in treating hyperplasia of mammary gland （HMG） and predict the potential mechanisms of action of core herbal combinations in treating HMG. Methods Outpatient electronic medical records for the diagnosis and treatment of HMG by Professor Zhou Zhongying were reviewed. The frequency， properties， flavors and meridian tropism of the included Chinese herbs were statistically analyzed，followed by association rule analysis and system clustering analysis to summarize the medication rule and identify core herbal combinations. Network pharmacology and molecular docking were employed to explore the potential mechanism of the core herbal combinations in treating HMG. Results A total of 145 patients，386 prescriptions，and 270 Chinese herbs were included. Frequency analysis showed that the herbs used by Professor Zhou in treating HMG were primarily cold and bitter in nature，with meridian tropism in liver. Association rule and system clustering analysis identified “Cyperi Rhizoma-Bupleui Radix-Prunellae Spica” as the core herbal combination. Network pharmacology analysis identified 37 active components in the core herbal combination and 122 potential therapeutic targets for HMG. Protein-protein interaction （PPI） network analysis identified 10 core targets，including signal transducer and activator of transcription 3 （STAT3），phosphoinositide 3-kinase regulatory subunit 1 （PIK3R1），and estrogen receptor 1 （ESR1）. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis indicated that the active components of the core herbal combination primarily exert effects through pathways such as PI3K-Akt， Ras， and EGFR， and are closely associated with central carbon metabolism and proteoglycan pathways in cancer. Molecular docking results demonstrated good binding capacity and stability between ESR1，SRC，AKT1 and β -sitosterol， as well as between ESR1 and luteolin. Conclusion Professor Zhou Zhongying’s treatment approach for HMG centers on addressing the essence of “liver depression”， focusing on regulating liver qi and unblocking the milk ducts， simultaneously clearing heat， resolving phlegm， and promoting blood circulation. The main components of the core herbal combination “Cyperi Rhizoma-Bupleui Radix-Prunellae Spica” are represented as luteolin and β -sitosterol， which act on targets such as AKT1 and ESR1， and exert therapeutic effects on HMG through pathways like PI3K-Akt，Ras，EGFR，and other cancer-related signaling pathways.

R285.6；R285.5

江苏省中医药管理局江苏省中医药科技发展计划项目（QN202003）；江苏省教育科学“十四五”规划重点课题（C-b/2021/01/15）；国家中医药管理局“国医大师周仲瑛传承工作室”建设项目（国中医药人教发〔2010〕59号）；江苏省科技厅社会发展重点研发计划项目（BE2019723）