目的 通過(guò)網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)探討異功散治療小兒厭食癥的主要成分及作用機(jī)制。方法 通過(guò)TCMSP數(shù)據(jù)庫(kù)查找異功散中口服利用度和類(lèi)藥性符合要求的化合物，并通過(guò)PubChem、UniProt數(shù)據(jù)庫(kù)獲得其已知靶點(diǎn)。通過(guò)GeneCards、OMIM、NCBI Gene、DisGeNET、TTD數(shù)據(jù)庫(kù)獲得小兒厭食癥相關(guān)靶點(diǎn)。將異功散和小兒厭食癥靶點(diǎn)取交集，并構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)。通過(guò)中心度值、緊密中心度值、節(jié)點(diǎn)連接度值進(jìn)一步篩選出關(guān)鍵靶點(diǎn)。將關(guān)鍵靶點(diǎn)蛋白進(jìn)行基因本體論（GO）功能和京都基因與基因組百科全書(shū)（KEGG）通路富集分析。采用PyMOL和AutoDock Vina軟件將關(guān)鍵靶點(diǎn)和化合物進(jìn)行分子對(duì)接。結(jié)果 異功散中共獲得139個(gè)符合條件的化合物，相對(duì)應(yīng)781個(gè)靶點(diǎn)，小兒厭食癥共獲得靶點(diǎn)2278個(gè)，二者交集為369個(gè)靶點(diǎn)。通過(guò)PPI網(wǎng)絡(luò)構(gòu)建得到66個(gè)關(guān)鍵靶點(diǎn)，關(guān)鍵靶點(diǎn)的GO功能注釋和KEGG通路富集分析得出生長(zhǎng)因子應(yīng)答、轉(zhuǎn)錄調(diào)節(jié)、癌癥通路和蛋白磷酸化通路等生化過(guò)程和信號(hào)通路與異功散治療小兒厭食癥具有相關(guān)性。分子對(duì)接結(jié)果表明山柰酚、槲皮素、柚皮素、戈米辛B、12-異戊烯?；?2E,8E,10E-白術(shù)三醇與甘油醛-3-磷酸脫氫酶（GAPDH）、絲氨酸/蘇氨酸蛋白激酶1（AKT1）、白蛋白（ALB）、P53核內(nèi)磷酸化蛋白（TP53）、腫瘤壞死因子（TNF）、白細(xì)胞介素-6（IL-6）等靶點(diǎn)具有較好結(jié)合能力。結(jié)論 異功散通過(guò)調(diào)節(jié)絲裂原活化蛋白激酶（MAPK）、核因子-κB（NF-κB）、生長(zhǎng)因子、癌癥、蛋白磷酸化等相關(guān)的信號(hào)通路來(lái)實(shí)現(xiàn)對(duì)胃腸道消化功能和腸道菌群的調(diào)節(jié)從而治療小兒厭食癥。

Objective To explore the main ingredients and mechanism of Yigongsan in treatment of pediatric anorexia through network pharmacology and molecular docking technology. Methods Compounds that met the requirements of oral availability and drug-like properties in Yigongsan were searched through TCMSP database, and their targets were obtained through PubChem, UniProt databases. Targets related to pediatric anorexia were obtained through GeneCards, OMIM, NCBI Gene, DisGeNET and TTD databases. The intersection of Yigongsan and pediatric anorexia targets was obtained and protein-protein interaction network (PPI) was constructed. Key targets were further screened by betweenness centrality, closeness centrality, and degree. Key target proteins were analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment. PyMOL and AutoDock Vina software were used to conduct molecular docking between key targets and compounds. Results A total of 139 qualified compounds were obtained from Yigongsan corresponding to 781 targets, and 2278 targets were obtained from pediatric anorexia. The intersection of the two was 369 targets. A total of 66 key targets were obtained through the PPI network. The GO functional annotation and KEGG pathway enrichment analysis of key targets showed that biochemical processes and signaling pathways such as growth factor response, transcriptional regulation, cancer pathway and protein phosphorylation pathway were correlated with the treatment of pediatric anorexia by Yigongsan. The molecular docking results showed that kaempferol, quercetin, naringenin, gomisin B, 12-senecioyl-2E,8E,10E-atractylentriol had good binding ability to GAPDH, AKT1, ALB, TP53, TNF, IL-6 and other targets. Conclusion Yigongsan can regulate gastrointestinal digestive function and intestinal flora by regulating MAPK, NF-κB, growth factor, cancer, protein phosphorylation and other related signal pathways to treat pediatric anorexia.

R285

中央引導(dǎo)地方科技發(fā)展資金項(xiàng)目（206Z2502G）