目的 挖掘药食同源类中药治疗糖尿病足（diabetic foot，DF）的用药规律并探究其潜在分子机制，为开发针对DF的药膳疗法提供指导。方法 通过检索中国知网、万方数据库和中国生物医学文献数据库中中药方剂治疗DF的临床文献，将其中药名称规范化后与药食同源类中药名单比较，得到药食同源来源方药集；采用中医传承辅助系统分析其用药规律，根据关联规则和聚类分析确定对DF具有治疗作用的药食同源类核心中药；获取核心中药的活性成分及其治疗DF的作用靶点，进行蛋白质相互作用（protein-protein interaction，PPI）分析以及基因本体（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析；利用分子对接及动力学模拟，评估主要活性成分与其对应靶点的结合能力及结合稳定性。结果 共筛选出药食同源类中药方剂521条，其性温平，味甘苦，入心、脾经，以补虚和清热药为主；进一步分析得到具有强关联性组合药对4个，获得4个治疗DF的药食同源潜在新组方药；筛选出当归、黄芪、金银花、甘草和桃仁为治疗DF的药食同源类核心中药，其作用机制主要涉及高级糖基化终末产物-受体（advanced glycation end products，AGE-RAGE）、缺氧反应因子-1（hypoxia-inducible factor-1，HIF-1）、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等信号通路；核心中药包含的主要活性成分槲皮素和β-谷甾醇分别与治疗DF的关键靶点蛋白基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）及氧化物酶体增殖物激活受体γ（peroxisome proliferator activated receptor γ，PPARγ）具有较好的结合能力及稳定性。结论 药食同源类中药主要通过调节气血凝滞、筋脉阻塞等病机发挥治疗DF的作用，其关键活性成分可通过作用于DF主要治疗靶点MMP9、PPARγ等，进而调节AGE-RAGE、HIF-1和胰岛素抵抗等信号通路协同治疗DF，“黄芪-金银花-甘草”是极具潜力的DF药膳疗法新组方。

Objective To explore the medication rules and potential molecular mechanisms of medicinal and food homologous traditional Chinese medicine in the treatment of diabetic foot (DF), and provide guidance for the development of medicated diet therapy for DF. Methods Related clinical literature on Chinese medicine prescription for treating DF was screened from CNKI, Wanfang data and China Biology Medicine disc. Then the traditional Chinese medicine name was standardized to make them into structured data for intersected with medicinal and food homologous traditional Chinese medicine list to set up medicinal and food homologous formula database. The traditional Chinese medicine inheritance auxiliary platform was employed to analyze the medication rule, the medicinal and food homologous core traditional Chinese medicines were determined to have the therapeutic effect on DF by association rules and cluster analysis. The active components of core traditional Chinese medicines and their therapeutic targets for DF were obtained, and protein-protein interaction (PPI) analysis, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted. Molecular docking and kinetic simulation were used to evaluate the binding ability and stability of the main active components and their corresponding targets. Results A total of 521 medicinal and food homologous traditional Chinese medicine prescriptions containing homology medicines were selected, which were warm and neutral, sweet and bitter taste, and entering the heart and spleen meridians, mainly tonifying deficiency and clearing heat. Then, four highly correlated combination drug pairs and four potential new prescriptions in the treatment of DF were obtained. Danggui (Angelicae Sinensis Radix), Huangqi (Astragali Radix), Jinyinhua (Lonicerae Japonicae Flos), Gancao (Glycyrrhizae Radix et Rhizoma), Taoren (Persicae Semen) were selected as the medicinal and food homologous core traditional Chinese medicines for treating DF, and their mechanism of action mainly involved advanced glycation end products (AGE-RAGE), hypoxia-inducible factor-1 (HIF-1), mitogen-activated protein kinase (MAPK) and other signaling pathways. Quercetin and β-sitosterol, as the core active constituents, showed high binding affinity and stability with key target protein matrix metalloproteinase 9 (MMP9) and peroxisome proliferator activated receptor γ (PPARγ), respectively. Conclusion Medicinal and food homology traditional Chinese medicines mainly targeted the phenomenon of stagnation of qi and blood and obstruction of tendons and veins to treat DF, the key active components can act on the main therapeutic targets of DF, such as MMP9 and PPARγ, and then regulate the signaling pathways of AGE-RAGE, HIF-1 and insulin resistance to synergistically treat DF. “Astragali Radix-Lonicerae Japonicae Flos-Glycyrrhizae Radix et Rhizoma” is a potential prescription of DF medicated diet therapy.

广东省中医药局科研项目（20244044，20241171）；广东省医学科研基金项目（A2022168）