目的 通過構建升麻Cimicifugae Rhizoma化學成分-靶點-代謝信號通路網(wǎng)絡，探討其治療乳腺癌的作用機制。方法 利用中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）和PharmMapper獲取升麻化學成分與作用靶點，將其與乳腺癌疾病靶點取交集得到升麻治療乳腺癌的作用靶點，進一步利用靶點-成分反向篩選得到治療乳腺癌的升麻潛在活性成分；通過GeneMANIA數(shù)據(jù)庫獲取間接靶標和“蛋白-靶點”互作網(wǎng)絡，并通過蛋白-蛋白相互作用篩選關鍵靶標；采用Cytoscape構建“成分-靶點”網(wǎng)絡圖，使用分子對接將潛在活性成分和關鍵靶標配對，以證實前期靶標篩選和反向藥效團匹配的可靠性；通過DAVID網(wǎng)站對作用靶點進行基因本體論（GO）分析和京都基因與基因組百科全書（KEGG）分析，利用R語言和在線繪圖網(wǎng)站（omishare tools）將結果可視化。結果 獲得升麻潛在活性成分共68個，與乳腺癌相關疾病靶點48個，關鍵靶點為ESR1、SRC和HRAS。GO功能富集分析得到生物過程（BP）條目484條，細胞組成（CC）條目7條，分子功能（MF）條目75條。KEGG通路富集篩選獲得到21條信號通路。分子對接結果顯示關鍵靶標與升麻潛在活性成分匹配性較好。結論 升麻主要通過作用于ESR1、SRC、HRAS等靶點，調(diào)節(jié)癌癥通路、蛋白多糖通路和雌激素信號通路等起到治療乳腺癌的作用。

Objective To establish a chemical constituents-disease target-metabolic signaling pathway network of Cimicifugae Rhizoma for understanding its mechanism on anti-breast cancer. Methods TCMSP database and PharmMapper were used to obtain the chemical components and action targets of Cimicifugae Rhizoma. The therapeutic targets of anti-breast cancer were obtained by intersecting these targets above with those of breast cancer disease. Then, the reverse screening was executed for the potential active components of Cimicifugae Rhizoma. Indirect targets and protein-targets interaction networks were acquired through the GeneMANIA database, and key targets were screened through protein-protein interaction. Cytoscape was used to construct the "medicinal materia-ingredient-target" network diagram, and molecular docking was used to pair up potential active components with key targets, which confirmed the credibility of early target screening and reverse pharmacophore matching methods. Targets were imported into DAVID database for GO function enrichment analysis and KEGG pathway analysis, the results were visualized using R language and Omishare Tools. Results Tatolly 68 potential active ingredients of Cimicifugae Rhizoma and 48 breast cancerrelated disease targets were obtained, the key targets were ESR1, SRC, and HRAS. A total of 75 GO items were obtained by GO functional enrichment analysis, including 484 biological processes (BP), and seven cell component (CC) items. KEGG enrichment analysis yielded 21 pathways. The result of molecular docking suggested that key targets paired well with the potential active components of Cimicifugae Rhizoma. Conclusion Cimicifugae Rhizoma carried out its therapeutic means in breast cancer treatment mainly through its behaviors of acting on targets such as ESR1, SRC, HRAS, etc, and regulating pathways in cancer, proteoglycans in cancer, and estrogen signaling pathway.

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中國博士后科學基金面上項目（2018M633721）；遼寧省科技特派行動專項計劃（2020JH5/10400129）；遼寧省中藥資源普查項目（2019020）