目的 利用網(wǎng)絡(luò)藥理學(xué)和加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析（WGCNA）方法探討防己地黃湯治療類風(fēng)濕關(guān)節(jié)炎的分子機(jī)制。方法 利用TCMSP、SwissTargetPrediction、HERB數(shù)據(jù)平臺及相關(guān)文獻(xiàn)檢索防己地黃湯的主要活性成分及其相關(guān)靶點(diǎn)，通過R軟件limma包對GEO平臺類風(fēng)濕關(guān)節(jié)炎數(shù)據(jù)集GSE110169進(jìn)行差異分析。基于WGCNA篩選與疾病相關(guān)的基因模塊。利用R軟件VennDiagram包進(jìn)行交集靶點(diǎn)分析。通過Cytoscape的cytoHubba插件篩選核心靶點(diǎn)基因。采用Cytoscape軟件進(jìn)行“藥物-活性成分-靶點(diǎn)-疾病”網(wǎng)絡(luò)構(gòu)建與分析。clusterProfiler包對交集靶點(diǎn)基因進(jìn)行基因本體論（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路富集分析。通過PyMOL軟件對核心活性成分與核心靶點(diǎn)基因進(jìn)行分子對接驗(yàn)證；并運(yùn)用CIBERSOTR進(jìn)行核心靶點(diǎn)基因的免疫浸潤分析。結(jié)果 共篩選出有效活性成分129個，相關(guān)靶點(diǎn)1 280個，基因芯片差異基因2 091個；篩選出3個與疾病相關(guān)的基因模塊；獲得藥物與疾病共同靶點(diǎn)139個；KEGG通路分析顯示，主要富集在T細(xì)胞受體信號通路、NOD樣受體信號通路、Toll樣受體信號通路等；篩選出漢黃芩素和槲皮素2個核心成分及腫瘤蛋白53（TP53）和胱氨酸蛋白酶3（CASP3）2個核心靶點(diǎn)基因。分子對接顯示，核心成分與核心靶點(diǎn)之間均具有穩(wěn)定的結(jié)合能力；免疫浸潤分析表明，核心靶點(diǎn)基因與多數(shù)免疫細(xì)胞關(guān)系密切。結(jié)論 防己地黃湯可能從抗炎、調(diào)節(jié)免疫細(xì)胞功能等多方面發(fā)揮對類風(fēng)濕關(guān)節(jié)炎的治療作用。

Objective To investigate the molecular mechanism of Fangji Dihuang Decoction in treatment of rheumatoid arthritis based on network pharmacology and WGCNA. Methods The main active ingredients of Fangji Dihuang Decoction and their related targets were retrieved using TCMSP, SwissTargetPrediction, and HERB data platforms. And the difference analysis of GEO platform rheumatoid arthritis dataset GSE110169 was performed by R software limma package. Screening of gene modules associated with diseases based on WGCNA. Intersectional target analysis was performed using the R software VennDiagram package. Core target genes were screened by CytoHubba plugin of Cytoscape. Cytoscape software was used to construct and analyze the “drug-active component-target-disease” network. clusterProfiler package was used for GO and KEGG pathway enrichment analysis of intersectional target genes. Molecular docking of the core active ingredient with the core target genes was verified by PyMOL software, and immuno-infiltration analysis of the core target genes was performed by CIBERSOTR. Results A total of 129 active ingredients, 1 280 related targets, and 2 091 differential genes on gene chips were screened, 3 disease-related gene modules were screened, and 139 common targets between drugs and diseases were obtained. KEGG pathway analysis showed that they were mainly enriched in T cell receptor signaling pathway, NOD-like receptor signaling pathway, and Toll-like receptor signaling pathway. Two core components of wogonin and quercetin and two core target genes of tumor protein 53 (TP53) and cystine protease 3 (CASP3) were screened. Molecular docking showed that both core components and core targets had stable binding ability. Immune infiltration analysis showed that the core target genes were closely related to most immune cells. Conclusion Fangji Dihuang Decoction may exert therapeutic effects on rheumatoid arthritis in various aspects, including anti-inflammation and regulation of immune cell function.

R285

國家自然科學(xué)基金項(xiàng)目（82074090）