目的 應(yīng)用網(wǎng)絡(luò)藥理學(xué)方法對(duì)雷公藤多苷引起睪丸損傷機(jī)制進(jìn)行研究，探討潛在靶點(diǎn)和作用機(jī)制，并進(jìn)行動(dòng)物實(shí)驗(yàn)驗(yàn)證，為后續(xù)該藥物的合理使用提供新的研究策略。方法 依托文獻(xiàn)查詢和TCMSP、GeneCards、OMIM、Metascape數(shù)據(jù)庫挖掘雷公藤多苷中有效成分信息，挑選主要藥物活性成分及與睪丸損傷相關(guān)性靶點(diǎn)，構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)。使用Metascape數(shù)據(jù)庫對(duì)核心靶點(diǎn)進(jìn)行基因本體（GO）基因注釋及京都基因與基因百科全書（KEGG）通路富集分析，并進(jìn)行分子對(duì)接和動(dòng)物實(shí)驗(yàn)驗(yàn)證。結(jié)果 共篩選出雷公藤多苷18個(gè)活性成分，其中雷酚萜醇、苯代南蛇堿、雷公藤對(duì)醌A等為主要活性成分；雌激素受體1（ESR1）、表皮生長(zhǎng)因子受體（EGFR）等為核心靶點(diǎn)；KEGG富集分析雷公藤多苷活性成分作用于睪丸損傷的通路主要涉及癌癥信號(hào)通路、cAMP信號(hào)通路、Ras信號(hào)通路等；網(wǎng)絡(luò)藥理學(xué)與分子對(duì)接結(jié)果分析顯示呋喃南蛇堿與蛋白激酶B1（Akt1）結(jié)合良好，雷公藤對(duì)醌A與腫瘤壞死因子（TNF）結(jié)合良好，苯代南蛇堿與ESR1結(jié)合良好；動(dòng)物實(shí)驗(yàn)中雷公藤多苷組ESR1、EGFR mRNA表達(dá)水平顯著升高（P＜0.05）。結(jié)論 雷公藤多苷致睪丸損傷的機(jī)制可能與核心靶點(diǎn)ESR1、EGFR等密切相關(guān)。

Objective To investigate the mechanism of testicular injury induced by tripterygium glycosides by network pharmacology, explore the potential targets and mechanism of action, and conduct animal experiments to verify it, so as to provide a new research strategy for the rational use of the drug. Methods Based on literature search and TCMSP, GeneCards, OMIM, and Metascape databases, the information of active ingredients in tripterygium glycosides was mined, and the main active ingredients and targets associated with testicular injury were selected to construct the protein interaction (PPI) network. Metascape database was used to conduct gene ontology (GO) gene annotation and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analysis for core targets, and molecular docking and animal experiments were conducted. Results A total of 18 active components of tripterygium glycosides were screened, among which the main active components were triptonoterpenol, celabenzine, triptoquinone A. Estrogen receptor 1 (ESR1) and epidermal growth factor receptor (EGFR) were the core targets. KEGG enrichment analysis of the active components of tripterygium glycosides on testicular injury mainly involved cancer signaling pathway, cAMP signaling pathway, Ras signaling pathway, etc. The results of network pharmacology and molecular coupling analysis showed that celafurine was well bound to protein kinase B1 (Akt1), triptoquinone A was well bound to tumor necrosis factor (TNF), and celabenzine was well bound to ESR1. The mRNA expression levels of ESR1 and EGFR in tripterygium glycosides group were significantly increased (P < 0.05). Conclusion Mechanism of testicular injury induced by tripterygium glycosides may be closely related to the core targets such as ESR1 and EGFR.

R285；R287.3