目的 利用网络药理学及分子对接探究消渴清颗粒治疗糖尿病前期的作用机制。方法 通过中药系统药理学数据库搜索有关于消渴清颗粒中中药的有效成分与靶点，在GeneCards数据库、OMIM数据库搜索糖尿病前期的基因靶点，进而获得药物-疾病交集靶点，将交集靶点导入String蛋白质相互作用数据库和Cytoscape构建蛋白质相互作用（PPI）网络图，并筛选核心靶点，再将药物-疾病交集靶点导入DAVID数据库，对其分别进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，筛选出与疾病相关的通路，通过Cytoscape得出“通路-靶点”网络图，再通过插件分析得出“通路-靶点”网络核心靶点，取二者度值排名前7位的靶点交集作为消渴清颗粒治疗糖尿病前期的关键靶点，最后选择关键靶点与有效成分用AutoDock与Pymol软件进行分子对接及可视化。结果 筛选出消渴清颗粒中药活性成分36种，其中筛选出6种关键活性成分，分别为槲皮素、山柰酚、小檗碱、β-谷甾醇、花生四烯酸、知母皂苷C，靶点基因232个；筛选出糖尿病前期靶点685个，交集靶点93个，关键靶点5个，分别为肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、蛋白激酶B1（Akt1）、白细胞介素-1β（IL-1β）、环加氧酶2（PTGS2）。GO通路富集主要涉及内容有炎症、药物反应，细胞生长凋亡等；KEGG通路富集分析显示糖尿病并发症中的晚期搪基化终产物及其受体（AGE-RAGE）信号通路、TNF信号通路、缺氧诱导因子-1（HIF-1）信号通路、IL-17信号通路、胰岛素抵抗通路、磷脂酰肌醇3-激酶（PI3K）/Akt信号通路等，分子对接结果显示关键靶点与有效成分具有较稳定的结合能力。结论 消渴清颗粒中各种药物成分通过多靶点、多通路协同治疗糖尿病前期的作用机制，为进一步研究治疗糖尿病提供了线索。

Objective To explore the mechanism of Xiaokeqing Granules in treatment of prediabetes using network pharmacology and molecular docking. Methods The active ingredients and targets of Xiaokeqing Granules were searched in the Chinese medicine system pharmacology database, and the gene targets of prediabetes were searched in the GeneCards database and OMIM database, and the drug-disease intersection targets were obtained. The intersection targets were imported into string protein interaction database and Cytoscape to construct protein-protein interaction networks (PPI) network map, and the core targets were screened, and then the intersection targets of drug-disease were imported into DAVID database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed to screen out disease-related pathways, and the “pathway-target” network diagram was obtained by Cytoscape. The core targets of the “pathway-target” network were obtained by plug-in analysis, and the intersection of the top 7 targets with the degree value of the two was taken as the key targets for the treatment of pre-diabetes. Finally, the key targets and active ingredients were selected for molecular docking and visualization by AutoDock and Pymol software. Results A total of 36 active ingredients of Xiaokeqing Granules were screened out, of which 6 key active ingredients were screened out, including quercetin, kaempferol, berberine, β-sitosterol, arachidonic acid, and asoside C. 232 target genes, 685 pre-diabetic targets, 93 intersection targets, and 5 key targets were screened out. These were TNF, IL-6, Akt1, IL-1β, and PTGS2. GO pathway enrichment was mainly involved in inflammation, drug response, cell growth and apoptosis. KEGG pathway enrichment analysis showed AGE-RAGE signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, IL-17 signaling pathway, insulin resistance pathway, PI3K/Akt signaling pathway in diabetic complications. Molecular docking results showed that the key targets had stable binding ability with active ingredients. Conclusion The results show that the various drug components in Xiaokeqing Granules treat prediabetes through multi-target and multi-pathway cooperation, which provides clues for further research and treatment of prediabetes.

R285.5

安徽省卫生健康科研项目（AHWJ2023BAc10002）；安徽省高等学校科学研究项目（2023AH050782）；安徽省高等学校省级质量工程项目（2021jyxm0834）；新安医学与中医药现代化研究所“揭榜挂帅”项目（2023CXMMTCM024，2023CXMMTCM003）；糖脂代谢病教育部重点实验室开放基金项目（GYDKFXM01)；安徽省名中医方朝晖工作室（2019-8-515）；安徽省高校优秀拔尖人才培育项目（2022-371）；安徽中医药大学临床科研项目（2021yfylc01）；安徽省卫生健康骨干人才培养对象（2022-392）；2023年度新时代育人省级质量工程项目（研究生教育）建设项目（2023gjxslt014）