目的 基于網(wǎng)絡(luò)藥理學方法和分子對接技術(shù)探討褪黑素治療多囊卵巢綜合征的作用機制。方法 使用PubChem、Swiss Target Prediction、Pharm Mapper、DrugBank、TCMSP數(shù)據(jù)庫篩選褪黑素作用靶點，GeneCards、OMIM、DisGeNET數(shù)檢索多囊卵巢綜合征相關(guān)靶點，使用韋恩圖工具取交集，獲得褪黑素與多囊卵巢綜合征的共同靶點。構(gòu)建靶點蛋白互相作用（PPI）網(wǎng)絡(luò)，并篩選核心靶點，并進行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析，使用Cytoscape 3.7.1構(gòu)建褪黑素治療多囊卵巢綜合征的“靶點–信號通路”網(wǎng)絡(luò)圖。選擇主要靶標與褪黑素進行分子對接評價結(jié)合性。結(jié)果 褪黑素中109個有效靶點作用于多囊卵巢綜合征，關(guān)鍵核心靶點為SRC、PIK3R1、PIK3CA、EGFR、HRAS、RHOA、ERBB2、IGF1、MET、JAK2。富集的GO生物過程主要包括腺體發(fā)育、磷脂酰肌醇介導(dǎo)信號素、蛋白激酶B信號傳導(dǎo)等，富集的KEGG通路主要包括黏著斑、胰島素信號通路、趨化因子信號通路、孕酮–介導(dǎo)卵母細胞成熟等。分子對接結(jié)果顯示，褪黑素與核心靶點PIK3R1、PIK3CA、EGFR、HRAS、RHOA、ERBB2、MET、JAK2結(jié)合較好。結(jié)論 褪黑素可能通過抗凋亡、調(diào)節(jié)代謝、抑制炎癥反應(yīng)、抗氧化應(yīng)激等作用改善多囊卵巢綜合征。

Objective To explore the mechanism of melatonin in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking technology.Methods PubChem,Swiss Target Prediction,Pharm Mapper,DrugBank,TCMSP were used to screen melatonin targets.GeneCards,OMIM,DisGeNET databases were used to obtain polycystic ovary syndrome related targets.The Venn diagram tool was used to obtain the common target of melatonin and polycystic ovary syndrome.The target protein interaction (PPI) network was constructed,and the core targets were screened,and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed.Cytoscape 3.7.1 was used to construct the"target-signaling pathway"network map of melatonin treatment in polycystic ovary syndrome.The main target and melatonin were selected for molecular docking evaluation.Results 109 Effective targets of melatonin act on polycystic ovary syndrome,and the key core targets are SRC,PIK3R1,PIK3CA,EGFR,HRAS,RHOA,ERBB2,IGF1,MET,and JAK2.The enriched GO biological processes mainly included gland development,phosphtidylinositol mediated signaling hormone,protein kinase B signaling,etc.The enriched KEGG pathways mainly included adhesion plaque,insulin signaling pathway,chemokine signaling pathway,progesterone-mediated oocyte maturation,etc.Molecular docking results showed that melatonin binds well to the core targets PIK3R1,PIK3CA,EGFR,HRAS,RHOA,ERBB2,MET,and JAK2.Conclusion Melatonin may improve polycystic ovary syndrome by anti-apoptosis,regulating metabolism,inhibiting inflammation and anti-oxidative stress.

R984

國家自然科學基金資助項目(81674011);中國中醫(yī)科學院科技創(chuàng)新工程(CI2021A02404)