目的 基于網(wǎng)絡(luò)藥理學(xué)研究人參對非酒精性脂肪肝病（NAFLD）的治療靶點。方法 利用網(wǎng)絡(luò)藥理學(xué)分析平臺BATMAN-TCM獲取人參活性成分及其對應(yīng)靶點，使用Cytoscape軟件對功能組-靶點基因-人參藥物成分網(wǎng)絡(luò)進(jìn)行構(gòu)建。對靶基因通過STRING平臺構(gòu)建出靶點群蛋白互作網(wǎng)絡(luò)（protein protein interaction network，PPI），通過在線工具metascape對靶基因進(jìn)行通路富集分析。從高通量基因表達(dá)數(shù)據(jù)庫（Gene Expression Omnibus，GEO）下載人NAFLD轉(zhuǎn)錄組表達(dá)數(shù)據(jù)GSE89632，表達(dá)量進(jìn)行標(biāo)準(zhǔn)化處理，使用雙側(cè)非配對t檢驗來檢測表達(dá)差異的顯著性。結(jié)果 人參藥物成分對脂肪代謝有顯著影響，特別是脂肪酸降解。通過蛋白相互作用分析和通路富集分析，發(fā)現(xiàn)了31個人參藥物成分的關(guān)鍵靶基因（ACADM、SCD、ACACA、ACSL1、NR1H3、LEP、PPARA、ADIPOQ、NR1H4、CEBPA、HMGCR、SREBF1、TNF、SREBF2、ESR1、ABCA1、INS、AKT1、AVP、RXRA、HSD17B6、SRD5A2、UGT1A1、CYP19A1、PTGS2、CYP2E1、HTR2A、HSD17B1、EDN1、CCL5、AGTR1）和NAFLD發(fā)病過程緊密相關(guān)。其中胰島素（insulin，INS）的節(jié)點數(shù)量遠(yuǎn)高于其他靶基因，INS的mRNA表達(dá)量在NAFLD組織中顯著上調(diào)（P<0.000 1）。結(jié)論 INS可能是人參治療NAFLD的關(guān)鍵核心靶點之一。

Objective To study the drug-target-pathway and its mechanism of Panax ginseng active ingredients in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology. Methods BATMAN-TCM, a network pharmacological analysis platform, was used to obtain Panax ginseng active ingredients and their corresponding targets. Cytoscape software was used to construct a functional group-target gene-ginseng drug component network. Target group protein interaction network (PPI) was constructed by STRING platform for target genes. Metascape was an online tool for channel enrichment analysis of target genes. Human NAFLD transcriptome expression data GSE89632 was downloaded from the Gene Expression Omnibus (GEO) database. The expression level was standardized and the significance of expression difference was detected by bilateral unpaired t test. Results The components of Panax ginseng had significant effects on lipid metabolism, especially on fatty acid degradation. Through protein interaction analysis and pathway enrichment analysis, 31 key target genes (ACADM, SCD, ACACA, ACSL1, NR1H3, LEP, PPARA, ADIPOQ, NR1H4, CEBPA, HMGCR, SREBF1, TNF, SREBF2, ESR1, ABCA1, INS, AKT1, AVP, RXRA, HSD17B6, SRD5A2, UGT1A1, CYP19A1, PTGS2, CYP2E1, HTR2A, HSD17B1, EDN1, CCL5, AGTR1) of Panax ginseng drug components were found to be involved in NAFLD pathway, which were closely related to the pathogenesis of NAFLD. The number of INS nodes was much higher than other target genes. The expression of INS was significantly up-regulated in NAFLD tissues (P<0.000 1). Conclusion Ginseng has therapeutic effect on NAFLD, and INS may be the key target of ginseng in the treatment of NAFLD.

R285.5

廣東省中醫(yī)藥管理局面上科研項目（20171274）；廣東省基礎(chǔ)與應(yīng)用基礎(chǔ)研究基金（2019A1515110369）