目的 應(yīng)用網(wǎng)絡(luò)藥理學(xué)和分子對接的方法探索丹參治療乳腺癌的作用靶點及分子機(jī)制。方法 由TCMSP數(shù)據(jù)庫檢索丹參的活性成分，由GeneCards、OMIM、TTD數(shù)據(jù)庫篩選乳腺癌的作用靶點，使用Cytoscape軟件構(gòu)建“成分-疾病-靶點”網(wǎng)絡(luò)圖。由STRING平臺構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)。通過DAVID數(shù)據(jù)庫進(jìn)行基因本體（GO）功能和京都基因與基因組百科全書（KEGG）通路富集分析，再由AutoDock Vina軟件完成活性成分與核心靶點的分子對接驗證，計算結(jié)合能，最終通過PyMol軟件將對接結(jié)果可視化。結(jié)果 篩選出丹參成分的對應(yīng)靶點114個，疾病靶點2 488個，得到共同靶點67個。富集分析表明共同靶點主要參與RNA轉(zhuǎn)錄、基因表達(dá)、細(xì)胞增殖與凋亡等生物過程，包括大分子復(fù)合物、細(xì)胞核、細(xì)胞質(zhì)等細(xì)胞組分，具有酶結(jié)合、蛋白質(zhì)結(jié)合、蛋白磷酸酶結(jié)合等分子功能，參與癌癥通路、前列腺癌、脂質(zhì)和動脈粥樣硬化、磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信號通路等。分子對接結(jié)果表明，木犀草素、隱丹參酮、二氫丹參酮Ⅰ、丹參酮Ⅱ_A與關(guān)鍵靶點Akt1、腫瘤抑制基因（TP53）、表皮生長因子受體（EGFR）、腫瘤壞死因子（TNF）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、血管內(nèi)皮生長因子A（VEGFA）的分子對接結(jié)合能均小于−5 kJ/mol。結(jié)論 木犀草素、隱丹參酮、二氫丹參酮Ⅰ、丹參酮Ⅱ_A是中藥丹參的主要成分，通過AKT1、TP53、EGFR、TNF、CASP3、VEGFA等關(guān)鍵靶點，調(diào)節(jié)癌癥通路、PI3K/Akt信號通路等發(fā)揮抗乳腺癌的作用。

Objective To explore mechanism of Salviae Miltiorrhizae Radix et Rhizoma in treatment of breast cancer based on network pharmacology and molecular docking. Methods The active ingredients of Salviae Miltiorrhizae Radix et Rhizoma were searched by TCMSP database, the targets of breast cancer were collected from GeneCards, OMIM, and TTD databases, and Cytoscape software was employed to establish the "composition-disease-targets" network. The PPI network was constructed by STRING platform and the map was visualized. DAVID database was used for GO function and KEGG pathway enrichment, then AutoDock Vina software was used for molecular docking to predict the binding performance of active ingredients and core targets, the results were visualized by PyMol software ultimately. Results 114 Corresponding targets for Salviae Miltiorrhizae Radix et Rhizoma and 2 488 disease targets were screened out, 67 common targets were obtained. The results of GO enrichment analysis showed that common targets were mainly involved in biological process such as RNA transcription, gene expression and apoptosis, cellular component such as macromolecular complex, nucleus and cytoplasm, molecular function such as enzyme binding, protein binding and protein phosphatase binding. KEGG enrichment analysis mainly point to pathways in cancer, prostate cancer, lipid and atherosclerosis, PI3K/Akt signaling pathway, etc. Molecular docking results revealed that luteolin, tanshinone Ⅱ_A, cryptotanshinone, and dihydrotanshinone Ⅰ can be tightly bonded with core targets Akt1, TP53, EGFR, TNF, CASP3, and VEGFA, the binding energy was less than −5 kJ/mol. Conclusion Luteolin, tanshinone Ⅱ_A, cryptotanshinone, and dihydrotanshinone Ⅰ are the core active compounds of Salviae Miltiorrhizae Radix et Rhizoma These ingredients play a role in treatment of breast cancer through key targets, by regulating cancer pathways, PI3K/Akt signaling pathways, etc.

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國家自然科學(xué)基金資助項目（81673764）；教育部產(chǎn)學(xué)合作協(xié)同育人項目（220906291010203）