目的 通過網(wǎng)絡(luò)藥理學方法探討四妙勇安湯對脫疽、糖尿病和冠心病“異病同治”的作用機制。方法 通過中藥系統(tǒng)藥理學分析平臺（TCMSP）數(shù)據(jù)庫檢索四妙勇安湯中4味中藥相關(guān)的所有化合物和作用靶點，運用UniProt數(shù)據(jù)庫進行標準化，并用Cytoscape 3.7.2軟件構(gòu)建“中藥-化合物-靶點”作用網(wǎng)絡(luò)；通過GeneCards和NCBI數(shù)據(jù)庫獲取脫疽、糖尿病和冠心病的相關(guān)基因，并與藥物作用靶點取交集，利用Cytoscape 3.7.2，構(gòu)建四妙勇安湯與3?。摼?、糖尿病、冠心?。┑陌悬c關(guān)聯(lián)網(wǎng)絡(luò)。通過STRING數(shù)據(jù)庫構(gòu)建共有靶點的PPI網(wǎng)絡(luò)；應用BioGPS獲取其在器官組織的分布信息，繪制關(guān)鍵共有靶點的人體定位圖譜?；贐ioconductor，進行GO功能富集和KEGG通路分析。結(jié)果 根據(jù)口服生物利用度≥ 30%和類藥性≥ 0.18，篩選得四妙勇安湯活性化合物，共計120個，并預測到205個潛在靶點；獲得脫疽疾病靶點946個，糖尿病疾病靶點14 957個，冠心病疾病靶點7 567個，將其映射到藥物作用靶點，獲得79個共有靶點。BioGPS顯示關(guān)鍵共有靶點主要分布在垂體、心臟、視網(wǎng)膜、腎上腺皮質(zhì)、骨骼肌中；GO功能富集分析得到條目93個（P<0.01），KEGG通路富集分析篩選得到147條信號通路（P<0.01）。糖尿病并發(fā)癥AGE-RAGE信號通路、動脈粥樣硬化與流體剪切應力、IL-17信號通路、TNF信號通路、Th17細胞分化、Toll樣受體信號通路等排序靠前，主要與免疫炎癥、細胞凋亡相關(guān)。結(jié)論 四妙勇安湯“異病同治”脫疽、糖尿病和冠心病的主要機制涉及免疫調(diào)節(jié)、炎癥反應以及細胞凋亡相關(guān)信號通路，為進一步實驗驗證、潛在藥理學機制及臨床拓展應用提供參考依據(jù)。

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.

北京市雙一流高層次人才科研經(jīng)費資助項目（1000041510053）