目的 基于网络药理学结合GEO数据库多芯片研究糖痹外洗方治疗糖尿病足相关疾病的潜在治疗靶点及可能作用机制。方法 采用TCMSP、TCMIP、TCMID、HERB数据库筛选糖痹外洗方化学成分及作用靶点。在GEO数据库中检索糖尿病足及相关疾病差异表达基因，汇总得到糖尿病足靶点。使用微生信在线作图平台对疾病靶点和化学成分靶点取交集，并构建交集靶点蛋白互相作用（PPI）网络。采用Metascape平台工具对交集靶点进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路分析。根据分析结果，选取度值排名靠前的化合物和蛋白，使用AutoDock Vina进行分子对接。结果 共得到糖痹外洗方活性成分99个，成分靶点427个，糖尿病足靶点2 217个，交集靶点64个。关键靶点蛋白主要有表皮生长因子受体（EGFR）、过氧化物酶体增殖物激活受体γ（PPARG）、环加氧酶2（PTGS2）、Janus激酶2（JAK2）、基质金属蛋白酶1（MMP1）等，关键成分有槲皮素、山柰酚、木犀草素等。GO功能富集分析得到665个生物过程、30个细胞组分、80个分子功能。KEGG通路富集分析共得到100条通路信息，主要有脂质与动脉粥样硬化通路、Janus激酶-信号传导及转录激活因子1（JAK-STAT）信号通路、磷脂酰肌醇-3-羟激酶（PI3K）-蛋白激酶B（Akt）信号通路、糖尿病并发症晚期糖基化终末产物/AGEs受体（AGE-RAGE）信号通路、核因子-κB（NF-κB）通路等。分子对接结果显示，地奥司明、鞣花酸、木犀草素、杨梅素和槲皮素与EGFR、JAK2、MMP1等关键靶点有较好的结合能力。结论 糖痹外洗方具有多成分、多靶点等特点，其可能主要作用于糖尿病并发症AGE-RAGE信号通路、脂质与动脉粥样硬化通路和JAK-STAT信号通路等的多个关键靶点，从而发挥治疗糖尿病足相关疾病的效果。

Objective To investigate the potential therapeutic targets and possible mechanism of Tangbi Waixi Prescription in treatment of diabetic foot-related diseases based on network pharmacology combined with GEO database multi-chip. Methods TCMSP, TCMIP, TCMID, and HERB database were used to screen the chemical constituents and targets of Tangbi Waixi Prescription. The differentially expressed genes of diabetic foot and related diseases were retrieved from GEO database, and the targets of diabetic foot were summarized. The intersection of disease targets and chemical component targets was obtained using the Weishengxin online mapping platform, and the intersection target protein interaction (PPI) network was constructed. Metascape platform tool was used to perform gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for intersection targets. According to the analysis results, the compounds and proteins with the highest degree value were selected, and AutoDock Vina was used for molecular docking. Results A total of 99 components and 427 targets of Tangbi Waixi Prescription, 2 217 targets of diabetic foot were retrieved, and 64 intersecting targets were identified. The major target proteins include EGFR, PPARG, PTGS2, JAK2, MMP1, and the key components include quercetin, kaempferol, luteolin, and diosmine. GO analysis yielded 665 biological processes, 30 cell components, and 80 molecular functions. KEGG pathway enrichment analysis yielded 100 signaling pathways which mainly related to lipid and atherosclerosis, JAK-STAT signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, NF-κB pathways, etc. The results of molecular docking showed that the diosmin, ellagic acid, luteolin, myricetin, quercetin had excellent binding abilities to EGFR, JAK2, MMP1 and other key targets. Conclusion Tangbi Waixi Prescription has the characteristics of multiple components and multiple targets, which may mainly act on the AGE-RAGE signaling pathway, lipid and atherosclerosis pathway, JAK-STAT signaling pathway, and other key targets of diabetic complications, so as to play a therapeutic effect on diabetic foot-related diseases.

R285.5

国家重点研发项目（2019YFC1709300，2019YFC1709305）