目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對接方法探討雷公藤治療狼瘡性腎炎的效毒作用機制。方法 通過TCMSP、Uniprot、STITCH等數(shù)據(jù)庫查詢雷公藤的化合物分子及其主要靶點，并與狼瘡性腎炎相關(guān)基因做對比，獲得藥物靶點與疾病相關(guān)的共有基因，構(gòu)建藥物與疾病之間的網(wǎng)絡(luò)關(guān)系。通過String數(shù)據(jù)庫獲取潛在作用靶標(biāo)之間的相互作用關(guān)系，利用Cytoscape軟件構(gòu)建中藥-成分-疾病網(wǎng)絡(luò)。運用Clusterprofiler程序分別進(jìn)行GO基因富集分析和KEGG通路富集分析。結(jié)果 從雷公藤中篩選得到44個候選活性成分，包括雷公藤甲素、雷公藤多苷、雷公藤紅素等；潛在作用靶標(biāo)228個，其中治療靶標(biāo)152個，毒性靶標(biāo)76個。GO富集分析結(jié)果顯示，治療靶標(biāo)主要與細(xì)菌來源分子的反應(yīng)（response to molecule of bacterial origin）、對脂多糖的反應(yīng)（response to lipopolysaccharide）、胞漿鈣離子濃度的正調(diào)控（positive regulation of cytosolic calcium ion concentration）等有關(guān)。治療狼瘡性腎炎的相關(guān)基因參與通路共125條，具有潛在不良反應(yīng)的相關(guān)基因通路共130條。分子對接結(jié)果表明，5 α-benzoyl-4α-hydroxy-1β，8α-dinicotinoyl-dihydro-agarofuran、triptofordin B1、triptofordinine A2與SYK有較好的結(jié)合性。結(jié)論 基于網(wǎng)絡(luò)藥理學(xué)方法和分子對接挖掘雷公藤對狼瘡性腎炎治療靶點和毒性靶點、治療作用通路和毒性作用通路，為研究雷公藤對狼瘡性腎炎效毒作用機制提供了新的研究方法。

Objective To explore the possible mechanism of Tripterygium wilfordii in treatment of lupus nephritis based on network pharmacology and molecular docking methods. Methods The main active components and the targets of Tripterygium wilfordii were searched and screened from TCMSP, Uniprot, and STITCH databases. By comparing with lupus nephritis related genes, common genes related to drug targets and diseases were obtained, and the network relationship between drugs and diseases was constructed. The interaction relationship between potential targets was obtained by String database, and the network of TCM-component-disease was constructed by Cytoscape software. Clusterprofiler program was used to analyze GO gene enrichment and KEGG pathway enrichment respectively. Results Forty-four candidate active ingredients were screened from Tripterygium wilfordii, mainly including triptolide, tripterygium glycosides, and celastrol. There were 228 potential targets, including 152 therapeutic targets and 76 bacterial origin, response to lipopolysaccharide, positive regulation of cytosolic calcium ion concentration. There were 125 related gene pathways involved in the treatment of lupus nephritis, and 130 related gene pathways with potential adverse reactions. Molecular docking results show that, 5 alpha-benzoyl-4alpha-hydroxy-1 beta, 8 Alpha-dinicotinoyl-Dihydro-Agarofuran, Triptofordin B1, Triptofordinine A2 showed good binding properties to SYK. Conclusion Based on the methods of network pharmacology and molecular docking, the therapeutic target, toxic target, therapeutic pathway and toxic pathway of Tripterygium wilfordii on lupus nephritis provide a new research method for the study of the mechanism of Tripterygium wilfordii.

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國家自然科學(xué)基金資助項目（82160938）；云南省衛(wèi)生健康委2020年高層次中醫(yī)藥后備人才（針灸治療慢性腎臟病方向）孵化項目（云衛(wèi)中醫(yī)發(fā)展發(fā)[2021]1號）；廣東省中醫(yī)藥局科研項目（20191287）；深圳市光明區(qū)科技局課題（GM2019010003）