目的 基于網(wǎng)絡(luò)藥理學(xué)結(jié)合GEO數(shù)據(jù)庫多芯片研究糖痹外洗方治療糖尿病足相關(guān)疾病的潛在治療靶點(diǎn)及可能作用機(jī)制。方法 采用TCMSP、TCMIP、TCMID、HERB數(shù)據(jù)庫篩選糖痹外洗方化學(xué)成分及作用靶點(diǎn)。在GEO數(shù)據(jù)庫中檢索糖尿病足及相關(guān)疾病差異表達(dá)基因，匯總得到糖尿病足靶點(diǎn)。使用微生信在線作圖平臺對疾病靶點(diǎn)和化學(xué)成分靶點(diǎn)取交集，并構(gòu)建交集靶點(diǎn)蛋白互相作用（PPI）網(wǎng)絡(luò)。采用Metascape平臺工具對交集靶點(diǎn)進(jìn)行基因本體（GO）分析和京都基因與基因組百科全書（KEGG）通路分析。根據(jù)分析結(jié)果，選取度值排名靠前的化合物和蛋白，使用AutoDock Vina進(jìn)行分子對接。結(jié)果 共得到糖痹外洗方活性成分99個，成分靶點(diǎn)427個，糖尿病足靶點(diǎn)2 217個，交集靶點(diǎn)64個。關(guān)鍵靶點(diǎn)蛋白主要有表皮生長因子受體（EGFR）、過氧化物酶體增殖物激活受體γ（PPARG）、環(huán)加氧酶2（PTGS2）、Janus激酶2（JAK2）、基質(zhì)金屬蛋白酶1（MMP1）等，關(guān)鍵成分有槲皮素、山柰酚、木犀草素等。GO功能富集分析得到665個生物過程、30個細(xì)胞組分、80個分子功能。KEGG通路富集分析共得到100條通路信息，主要有脂質(zhì)與動脈粥樣硬化通路、Janus激酶-信號傳導(dǎo)及轉(zhuǎn)錄激活因子1（JAK-STAT）信號通路、磷脂酰肌醇-3-羥激酶（PI3K）-蛋白激酶B（Akt）信號通路、糖尿病并發(fā)癥晚期糖基化終末產(chǎn)物/AGEs受體（AGE-RAGE）信號通路、核因子-κB（NF-κB）通路等。分子對接結(jié)果顯示，地奧司明、鞣花酸、木犀草素、楊梅素和槲皮素與EGFR、JAK2、MMP1等關(guān)鍵靶點(diǎn)有較好的結(jié)合能力。結(jié)論 糖痹外洗方具有多成分、多靶點(diǎn)等特點(diǎn)，其可能主要作用于糖尿病并發(fā)癥AGE-RAGE信號通路、脂質(zhì)與動脈粥樣硬化通路和JAK-STAT信號通路等的多個關(guān)鍵靶點(diǎn)，從而發(fā)揮治療糖尿病足相關(guān)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

國家重點(diǎn)研發(fā)項目（2019YFC1709300，2019YFC1709305）