目的 利用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)研究化橘紅抗酒精性肝損傷的潛在分子作用機(jī)制。方法 在中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）中獲取化橘紅的有效成分以及成分靶點(diǎn)，使用GeneCards、OMIM、TTD和DisGenet數(shù)據(jù)庫獲取疾病靶點(diǎn)基因信息，借助韋恩圖選取活性成分靶點(diǎn)以及疾病靶點(diǎn)基因的交集獲取化橘紅治療酒精性肝損傷的潛在作用靶點(diǎn)；利用STRING數(shù)據(jù)庫構(gòu)建蛋白相互作用網(wǎng)絡(luò)（PPI），并采用Cytoscape軟件得到核心靶點(diǎn)網(wǎng)絡(luò)圖；最后使用Metascape數(shù)據(jù)庫對核心靶點(diǎn)進(jìn)行基因本體論（GO）功能富集和基因百科全書（KEGG）分析，利用AutoDock Tools進(jìn)行活性成分與核心靶點(diǎn)的分子對接驗(yàn)證。結(jié)果 得到10個有效成分、98個成分靶點(diǎn)基因和1 531個疾病靶點(diǎn)基因，兩者取交集后獲取67個交集靶點(diǎn)。利用STRING數(shù)據(jù)庫和Cytoscape軟件最終得到腫瘤蛋白p53（TP53）、前列腺素內(nèi)過氧化物酶2（PTGS2）、半胱氨酸蛋白酶3（CASP3）、轉(zhuǎn)錄因子AP-1（JUN）、蛋白激酶B1（AKT1）5個核心靶點(diǎn)。GO分析和KEGG分析分別獲得過氧化物酶體等50條目和脂質(zhì)、動脈粥樣硬化等20條信號通路。結(jié)論 化橘紅可通過多個成分作用于多個靶點(diǎn)發(fā)揮抗炎、抑制細(xì)胞凋亡等作用，進(jìn)而抑制酒精性肝損傷。

Objective To investigate the potential molecular mechanisms of Citri Grandis Exocarpium in treatment of alcoholic liver injury by network pharmacology and molecular docking. Methods The active components and component targets of Citri Grandis Exocarpium were obtained from the TCMSP, and the gene information of disease target was obtained from GeneCards, OMIM, TTD, and DisGenet databases. The potential targets of Citri Grandis Exocarpium in treatment of alcoholic liver injury were obtained by the intersection of active component targets and disease targets selected by Venn diagram. The protein interaction network (PPI) was constructed using STRING database, and Cytoscape software was used to obtain the core target network map. Finally, Metascape database was used for gene ontology (GO) functional enrichment and Gene Encyclopedia (KEGG) analysis of the core target, and AutoDock Tools was used to verify the molecular docking between the active ingredients and the core targets. Results 10 active components, 98 component target genes, and 1 531 disease target genes were obtained. 67 intersection targets were obtained after the intersection of the two genes. Five core targets including p53 (TP53), prostaglandin peroxidase 2 (PTGS2), cysteine protease 3 (CASP3), transcription factor AP-1 (JUN), and protein kinase B (AKT1) were obtained by using STRING database and Cytoscape software. GO analysis and KEGG analysis respectively obtained 50 signal pathways such as peroxisome and 20 signal pathways such as lipid and atherosclerosis. Conclusion Citri Grandis Exocarpium might exhibit anti-inflammatory and anti-apoptosis effects through multiple components acting on multiple targets, thus attenuating alcoholic liver injury.

R285

廣東省應(yīng)用型科技研發(fā)專項(xiàng)資金項(xiàng)目（2016B020239003）