目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)聯(lián)合加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析（WGCNA）探究雷公藤治療系統(tǒng)性紅斑狼瘡（systemic lupus erythematosus，SLE）的潛在作用機(jī)制。方法 利用TCMSP數(shù)據(jù)庫(kù)檢索雷公藤的主要活性成分，并挖掘活性成分相關(guān)靶點(diǎn)，通過(guò)GEO平臺(tái)下載SLE相關(guān)基因芯片GSE65391，使用R軟件limma包進(jìn)行差異分析，并運(yùn)用WGCNA篩選出的模塊基因作為疾病靶點(diǎn)基因。R軟件Venn Diagram包進(jìn)行交集分析并可視化。利用ADEx平臺(tái)對(duì)交集靶點(diǎn)基因的表達(dá)情況進(jìn)行Meta分析。采用R軟件clusterProfiler包對(duì)交集靶點(diǎn)基因進(jìn)行基因本體論（GO）功能富集和京都基因與基因組百科全書(shū)（KEGG）信號(hào)通路富集分析。采用Cytoscape軟件進(jìn)行“藥物–活性成分–共同靶點(diǎn)”網(wǎng)絡(luò)的構(gòu)建與分析。將交集靶點(diǎn)基因上傳至STRING數(shù)據(jù)庫(kù)，把結(jié)果數(shù)據(jù)導(dǎo)入至Cytoscape軟件構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)并篩選核心靶點(diǎn)基因。表達(dá)量分析、PPI分析、診斷效能分析被用于展示核心靶點(diǎn)基因的作用與臨床價(jià)值。采用PyMOL軟件對(duì)核心活性成分與核心靶點(diǎn)基因進(jìn)行分子對(duì)接驗(yàn)證。利用R軟件并通過(guò)CIBERSORT算法對(duì)樣本的免疫細(xì)胞分布進(jìn)行計(jì)算。結(jié)果 共篩選出有效活性成分50個(gè)，成分相關(guān)靶點(diǎn)690個(gè)，WGCNA關(guān)聯(lián)模塊基因1 215個(gè)；KEGG通路分析，主要涉及Toll樣受體等信號(hào)通路；篩選出山柰酚、雷公藤甲素、triptofordin B1、異落葉松脂素4個(gè)核心成分和SIRT1核心靶點(diǎn)基因。分子對(duì)接結(jié)果顯示，山柰酚和雷公藤甲素與SIRT1具有穩(wěn)定的結(jié)合能力。免疫浸潤(rùn)分析結(jié)果顯示，SIRTI主要通過(guò)抑制中性粒細(xì)胞發(fā)揮抗SLE作用。結(jié)論 雷公藤可能從抗炎、調(diào)節(jié)免疫細(xì)胞功能等多方面發(fā)揮對(duì)SLE的治療作用，為雷公藤治療SLE提供了研究思路和理論支撐。

Objective To explore the effect and potential mechanism of Tripterygium wilfordii Hook.f.in treatment of systemic lupus erythematosus (SLE) by network pharmacology combined with WGCNA.Methods The TCMSP database was used to retrieve the main active ingredients of Tripterygium wilfordii Hook.f.,and the active ingredient-related targets were mined through the database.The gene chip GSE65391 related to SLE was downloaded from the GEO platform,and the limma package of R software was used for differential analysis,and the module genes selected by WGCNA were used as disease target genes.R software Venn Diagram package for intersection analysis visualization.ADEx platform was used to perform Meta-analysis on the expression of intersection target genes.R software clusterProfiler package was used to perform gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis for intersection target genes.Cytoscape software was used to construct and analyze the"drug-active ingredient-common target"network.The intersection target genes were uploaded to STRING database,and the result data were imported into Cytoscape software to construct protein interaction network (PPI) and screen the core target genes.Expression analysis,protein interaction analysis,and diagnostic efficiency analysis were used to demonstrate the role and clinical value of core target genes.PyMOL software was used to verify the molecular docking between core active components and core target genes.R software and CIBERSORT algorithm were used to calculate the distribution of immune cells.Results A total of 50 active components,690 component-related targets,and 1 215 WGCNA association module genes were screened out.KEGG pathway analysis mainly involved Toll-like receptors and other signaling pathways.Four core components including kaempferol,triptolide,triptofordin B1,isocolonin,and SIRT1 core target genes were screened.The molecular docking results showed that kaempferol and reaginin had stable binding ability to SIRT1.The results of immune infiltration analysis showed that SIRTI exerted anti-SLE effect mainly by inhibiting neutrophils.Conclusion In this study,we found that Tripterygium wilfordii Hook.f.may exert its therapeutic effects on SLE from various aspects such as anti-inflammation and regulation of immune cell function,which provides research ideas and theoretical support for the treatment of SLE with Tripterygium wilfordii Hook.f..

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國(guó)家自然科學(xué)基金資助項(xiàng)目(82074090);中國(guó)博士后科學(xué)基金資助項(xiàng)目(2020M682051);安徽省自然科學(xué)基金資助項(xiàng)目(1808085MH298);安徽省博士后科研活動(dòng)資助項(xiàng)目(2021A480)