目的 采用網(wǎng)絡(luò)藥理學(xué)和分子對接探討痛風(fēng)舒片治療痛風(fēng)的潛在作用機(jī)制。方法 檢索中藥系統(tǒng)藥理學(xué)分析平臺挖掘痛風(fēng)舒片關(guān)鍵成分和對應(yīng)靶點(diǎn)；檢索PharmGKB、GeneCards、OMIM、TTD、DrugBank數(shù)據(jù)庫，篩選痛風(fēng)疾病靶點(diǎn)，使用R軟件Venn包，獲取痛風(fēng)舒片與痛風(fēng)的交集靶點(diǎn)基因。使用Cytoscape 3.8.0軟件構(gòu)建“中藥復(fù)方成分–靶點(diǎn)”網(wǎng)絡(luò)圖并篩選藥物核心成分；使用String平臺獲取交集靶點(diǎn)基因的蛋白互作（PPI）網(wǎng)絡(luò)，并使用Cytoscape 3.8.0軟件篩選核心靶點(diǎn)基因。應(yīng)用R軟件對交集靶點(diǎn)基因進(jìn)行GO功能和KEGG通路富集分析，應(yīng)用AutoDock Vina軟件進(jìn)行分子對接。結(jié)果 共挖掘出痛風(fēng)舒片關(guān)鍵成分38種，對應(yīng)靶點(diǎn)164個(gè)，痛風(fēng)疾病靶點(diǎn)1 554個(gè)，二者交集靶點(diǎn)基因66個(gè)。篩選出核心成分6種（槲皮素、β-谷甾醇、蘆薈大黃素、高車前素、澤蘭黃醇素、海波拉亭），核心靶點(diǎn)基因6種[V-rel網(wǎng)狀內(nèi)皮細(xì)胞過多癥病毒癌基因同源物A（RELA）、白細(xì)胞介素-1β（IL-1β）、蛋白激酶B1（AKT1）、絲裂原活化蛋白激酶1（MAPK1）、NF-κB抑制因子α（NFKBIA）、腫瘤蛋白p53（TP53）]。GO功能共富集1 963個(gè)條目，其中生物過程1 830個(gè)（涉及對脂多糖的反應(yīng)等），細(xì)胞組分27個(gè)（涉及膜筏等），分子功能106個(gè)（涉及磷酸酶結(jié)合等）；KEGG通路共富集154個(gè)條目，如白細(xì)胞介素（IL）-17、腫瘤壞死因子（TNF）等信號通路。所有核心成分與核心靶點(diǎn)蛋白的結(jié)合能均＜−5 kcal/mol，大部分結(jié)合能＜−7 kcal/mol。結(jié)論 痛風(fēng)舒片中核心成分槲皮素、β-谷甾醇、蘆薈大黃素等可通過作用于RELA、IL-1β、AKT1等核心靶點(diǎn)基因，對IL-17、TNF等信號通路進(jìn)行調(diào)控，從而發(fā)揮治療痛風(fēng)的作用。

Objective To explore the potential mechanism of Tongfengshu Tablets in treatment of gout by network pharmacology and molecular docking. Methods Key components and corresponding targets of Tongfengshu Tablets were explored by searching pharmacology analysis platform of TCM system. Target genes of gout disease were obtained by searching PharmGKB, GeneCards, OMIM, TTD, and DrugBank databases, the intersection target genes of Tongfengshu Tablets and gout were obtained by Venn package of R software. The network diagram of “TCM compound component-target” was constructed and the drug core components was screened by Cytoscape 3.8.0 software. The protein interaction network of intersecting target genes was obtained using String platform, and the core target genes were screened by Cytoscape 3.8.0 software. GO function and KEGG pathway enrichment analysis were performed on the intersection target genes by R software and molecular docking was performed by AutoDock Vina software. Results A total of 38 key components and 164 corresponding targets of Tongfengshu Tablets were excavated, 1 554 targets of gout disease were excavated, there were 66 intersection target genes. Six core components (quercetin, β-sitosterol, aloe-emodin, dinatin, eupatin, and hypolaetin) and six core target genes (RELA, IL-1β, AKT1, MAPK1, NFKBIA, and TP53) were screened out. A total of 1 963 items were enriched in GO function, including 1 830 biological processes (involving reaction to lipopolysaccharide, etc.), 27 cell components (involving membrane raft, etc.) and 106 molecular functions (involving phosphatase binding, etc.). A total of 154 items were enriched in KEGG pathway, such as interleukin (IL-17), tumor necrosis factor (TNF) and other signaling pathways. The binding energies of all core components and core target proteins were < −5 kcal/mol, and most of them were < −7 kcal/mol. Conclusion The core components of Tongfengshu Tablets, including quercetin, β-sitosterol, aloe-emotin, ect., can regulate Il-17, TNF and other signaling pathways by acting on core target genes such as RELA, IL-1β, AKT1, etc., so as to play a role in the treatment of gout.

R285

亳州市重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(bzzc2020020)