目的 通过网络药理学方法探讨四妙勇安汤对脱疽、糖尿病和冠心病“异病同治”的作用机制。方法 通过中药系统药理学分析平台（TCMSP）数据库检索四妙勇安汤中4味中药相关的所有化合物和作用靶点，运用UniProt数据库进行标准化，并用Cytoscape 3.7.2软件构建“中药-化合物-靶点”作用网络；通过GeneCards和NCBI数据库获取脱疽、糖尿病和冠心病的相关基因，并与药物作用靶点取交集，利用Cytoscape 3.7.2，构建四妙勇安汤与3病（脱疽、糖尿病、冠心病）的靶点关联网络。通过STRING数据库构建共有靶点的PPI网络；应用BioGPS获取其在器官组织的分布信息，绘制关键共有靶点的人体定位图谱。基于Bioconductor，进行GO功能富集和KEGG通路分析。结果 根据口服生物利用度≥ 30%和类药性≥ 0.18，筛选得四妙勇安汤活性化合物，共计120个，并预测到205个潜在靶点；获得脱疽疾病靶点946个，糖尿病疾病靶点14 957个，冠心病疾病靶点7 567个，将其映射到药物作用靶点，获得79个共有靶点。BioGPS显示关键共有靶点主要分布在垂体、心脏、视网膜、肾上腺皮质、骨骼肌中；GO功能富集分析得到条目93个（P<0.01），KEGG通路富集分析筛选得到147条信号通路（P<0.01）。糖尿病并发症AGE-RAGE信号通路、动脉粥样硬化与流体剪切应力、IL-17信号通路、TNF信号通路、Th17细胞分化、Toll样受体信号通路等排序靠前，主要与免疫炎症、细胞凋亡相关。结论 四妙勇安汤“异病同治”脱疽、糖尿病和冠心病的主要机制涉及免疫调节、炎症反应以及细胞凋亡相关信号通路，为进一步实验验证、潜在药理学机制及临床拓展应用提供参考依据。

Objective The aim of this paper was to explore the mechanism of Simiao Yong'an Decoction in treating digital gangrene (A special name for a disease in Traditional Chinese medicine, including thromboangitis obliterans, arteriosclerosis Obliterans and gangrene), diabetes and coronary heart disease with concept of "treating different diseases with same method" based on network pharmacology. Methods The TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database was used to search all the compounds and targets related to four traditional Chinese medicines in Simiao Yong'an Decoction, UniProt database was used to standardize the targets and Cytoscape 3.7.2 software was used to construct the network of "herbs-compounds-targets". Through GeneCards and NCBI databases, the targets of digital gangrene (thromboangitis obliterans, arteriosclerosis Obliterans and gangrene), diabetes and coronary heart disease were obtained, then the common targets were obtained by intersecting the herbal targets and disease targets. Cytoscape 3.7.2 was used to construct the target association network between Simiao Yong'an Decoction and the three diseases. A protein-protein interaction (PPI) network was constructed through the STRING database, and BioGPS was used to obtain their distribution information in organs and tissues. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted through Bioconductor. Results About 688 compounds of Simiao Yong'an Decoction were found by TCMSP database; 120 active compounds were screened out according to standard of oral bioavailability ≥ 30% and drug like index ≥ 0.18; 205 herbal targets were obtained. About 946 digital gangrene targets, 14 957 diabetes targets and 7 567 Coronary heart disease targets were obtained, and 79 common targets were obtained after intersection with herbal targets. BioGPS showed that the key common targets were mainly distributed in pituitary, heart, retina, adrenal cortex and skeletal muscle. GO function enrichment analysis yielded 93 GO entries (P<0.01), and KEGG pathway enrichment analysis generated 147 signal pathways (P<0.01). The top signaling pathways, such as age-rage signaling pathway of diabetic complications, atherosclerosis and fluid shear stress, IL-17 signaling pathway, TNF signaling pathway, Th17 cell differentiation, and Toll-like receptor signaling pathway, are mainly related to immune inflammation and apoptosis. Conclusion The main mechanism of Simiao Yong'an Decoction in treating digital gangrene, diabetes and coronary heart disease with concept of "treating different diseases with same method" was related to Immune regulation, inflammatory responses and apoptosis-related signaling pathways, providing reference for further experimental verification, potential pharmacological mechanism and clinical application.

北京市双一流高层次人才科研经费资助项目（1000041510053）