目的 利用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討大黃肝毒性的分子作用機制。方法 在TCMSP檢索大黃活性成分及文獻獲取潛在肝毒性成分，利用Swiss Target Prediction數(shù)據(jù)庫獲取成分靶點，通過GeneCards和OMIM數(shù)據(jù)庫獲取人類肝毒性相關(guān)靶點。利用STRING數(shù)據(jù)庫將Venn圖獲得成分與疾病共同靶標(biāo)進行（PPI）網(wǎng)絡(luò)分析，用Cytoscape軟件構(gòu)建“大黃成分–肝毒性作用靶點”網(wǎng)絡(luò)，并且利用DAVID數(shù)據(jù)庫進行基因本體（GO）功能富集和京都基因與基因組百科全書（KEGG）（KEGG）通路富集。將部分肝毒性核心成分和關(guān)鍵靶點進行分子對接。結(jié)果 共獲取大黃潛在肝毒性成分21種，對應(yīng)靶點724個，人類肝毒性相關(guān)靶點957個，大黃與肝毒性的共同靶點151個，核心成分可能是大黃酸、大黃酚、β-谷甾醇、大黃素-1-O-β-D-葡萄糖硫苷、大黃素甲醚二葡萄糖苷、蘆薈大黃素等，關(guān)鍵靶點可能是白蛋白（ALB）、蛋白激酶B1（Akt1）、腫瘤蛋白p53（TP53）等。KEGG通路顯示癌癥通路、前列腺癌通路等可能在大黃肝毒性中起關(guān)鍵作用。分子對接結(jié)果表明，大黃肝毒性核心成分與關(guān)鍵靶點對接良好。結(jié)論 大黃通過多成分、多靶點、多通路機制導(dǎo)致肝毒性作用。

Objective To explore the mechanism of hepatotoxicity of Rhei Radix et Rhizoma by network pharmacology and molecular docking. Methods Potential hepatotoxic components of rhubarb were retrieved from TCMSP and literature. The component target was obtained by Swiss Target Prediction database, and the human hepatotoxic related targets were obtained by GeneCards and OMIM databases. The components obtained from Venn diagram and disease common targets were analyzed using STRING database for PPI network analysis, the “Rhei Radix et Rhizoma - hepatotoxicity targets” network was constructed using Cytoscape software, and the GO and KEGG pathway enrichment were performed using DAVID database. Some of the core components of hepatotoxicity were moleculically docked with key targets. Results A total of 724 targets corresponding to 21 potential hepatotoxic components of Rhei Radix et Rhizoma, 957 targets related to human hepatotoxicity, and 151 common targets of Rhei Radix et Rhizoma and hepatotoxicity were obtained. The core components of rhubarb may be rhein, chrysophanol, β-sitosterol, emodin-1-O-β-D-glucoside, emodin methyl ether diglucoside, aloe emodin, etc. The key targets may be ALB, AKT1, TP53, etc. KEGG pathway showed 139 signaling pathways indicating that cancer pathway and prostate cancer pathway may play a key role in the hepatotoxicity of Rhei Radix et Rhizoma. The results of molecular docking showed that the core components of Rhei Radix et Rhizoma hepatotoxicity interacted well with key targets. Conclusion Rhei Radix et Rhizoma causes hepatotoxicity through a multi-component, multi-target-multi-pathway mechanism.

R285