【摘要】 目的：利用网络药理学方法探讨许润三教授自拟加味消瘰丸治疗子宫肌瘤（UF）的作用机制。方法：基于TCMSP、BATMAN数据库收集加味消瘰丸中药物的活性成分并预测其潜在的作用靶点，利用GeneCards、OMIM、DisGeNET数据库检索UF的相关疾病靶点，在Cytoscape 3.10.0软件中构建“中药-活性成分-疾病靶点”网络，基于STRING数据库构建加味消瘰丸治疗UF的蛋白质-蛋白质互作（PPI）网络，根据拓扑分析参数筛选加味消瘰丸治疗UF的核心靶点，利用DAVID数据库进行疾病与药物交集靶点的基因本体（GO）功能及京都基因与基因组百科全书（KEGG）通路富集分析。结果：通过筛选获得87种活性成分，其中槲皮素、木樨草素、山奈酚、汉黄芩素、藏花酸被确定为关联靶标最高的活性成分；通过Venny 2.1.0分析得到加味消瘰丸治疗UF的预测靶点193个，拓扑分析后根据度（degree）值确定p53、Akt1、ESR1、TNF、JUN、IL6、HSP90AA1、EGFR、CCND1、MAPK1为核心靶点。GO功能富集分析得到957个条目，其中生物过程（BP）包括717个条目，主要涉及基因的正调控、RNA聚合酶II启动子转录的表达正向调控、对外源性刺激的响应、细胞增殖的正向调控、转录的正向调控、DNA的模版化等；分子功能（MF）包括159个条目，主要涉及酶结合、同种蛋白质结合、蛋白结合、RNA聚合酶II转录因子活性、配体激活的序列特异性DNA结合、转录因子活性、序列特异性DNA结合等；细胞组分（CC）包括81个条目，主要涉及细胞外空间、大分子复合物、细胞外区域、染色质、RNA聚合酶II转录因子复合物。KEGG共富集178条通路，主要涉及癌症通路、糖尿病并发症中的AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、PI3K-Akt信号通路。结论：本研究为未来开发中药复方提供了理论依据，也为进一步研究加味消瘰丸对UF的作用机制提供了重要的参考和指导。更多还原

【Abstract】 Objective: To investigate the mechanism of Master Xu Runsan′s self-formulated Supplemented ScrofulaRemoving Pill(Jiawei Xiaolei Wan) in treating uterine fibroids(UF) using network pharmacology. Methods: Active ingredients of the herbs in Supplemented Scrofula-Removing Pill and their potential targets were collected from the TCMSP and BATMAN databases, while UF-related disease targets were retrieved from GeneCards, OMIM, and DisGeNET databases. A “herb-active ingredient-disease target” network was constructed using Cytoscape 3.10.0. The protein-protein interaction(PPI) network for Supplemented Scrofula-Removing Pill against UF was built via the STRING database. Core therapeutic targets were screened based on topological parameters(degree value). Functional enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways was performed on intersecting targets using the DAVID database. Results: Through screening, 87 active ingredients were identified, with quercetin, luteolin, kaempferol, wogonin, and crocetin exhibiting the highest target associations. Venny 2.1.0 analysis revealed 193 predicted targets for UF treatment; topological analysis identified p53, Akt1, ESR1, TNF, JUN, IL6, HSP90AA1, EGFR, CCND1, and MAPK1 as core targets(ranked by degree value). GO functional enrichment yielded 957 entries: biological processes(BP, 717 entries) involved positive regulation of gene expression, RNA polymerase II promoter transcription, response to exogenous stimuli, and DNA-templated transcription; molecular functions(MF, 159 entries) focused on enzyme binding, protein binding, and transcription factor activity; cellular components(CC, 81 entries) were enriched in extracellular space and chromatin. KEGG pathway enrichment identified 178 pathways, primarily including cancer pathways, AGERAGE signaling in diabetic complications, fluid shear stress and atherosclerosis, and the PI3K-Akt signaling pathway. Conclusion: This study provides a theoretical foundation for developing traditional Chinese medicine(TCM) compound formulas and offers critical insights for further mechanistic research on Supplemented Scrofula-Removing Pill in UF treatment.更多还原