目的 基于網(wǎng)絡(luò)藥理學(xué)及實驗驗證探討制首烏肝毒性的機制。方法 利用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）、中醫(yī)藥整合藥理學(xué)研究平臺（TCMIP v2.0）收集制首烏的活性成分和作用靶點。通過GeneCards和OMIM數(shù)據(jù)庫獲取肝損傷相關(guān)的靶點。用Venny圖篩選獲得兩者的共同靶標(biāo)后，利用STRING數(shù)據(jù)庫進行蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析，用Cytoscape軟件構(gòu)建藥物-成分-靶點網(wǎng)絡(luò)，并且利用R語言進行基因本體論（GO）富集分析和京都基因與基因組百科全書（KEGG）通路富集。利用體內(nèi)實驗進一步驗證何首烏不同炮制品的肝毒性。結(jié)果 分別獲取制首烏活性成分30個，肝毒性相關(guān)靶點527個，制首烏活性成分與肝損傷的共同靶點48個，包括JUN、MAPK1、CYP3A4等。KEGG通路分析篩選了135條相關(guān)信號通路，顯示非酒精性脂肪肝通路和TNF信號通路等可能在制首烏肝毒性中起關(guān)鍵作用。體內(nèi)實驗表明，炮制后的何首烏肝毒性有效減輕，以九蒸九曬法效果最好。結(jié)論 制首烏肝毒性具有多成分、多靶點、多通路協(xié)同作用的特點，九蒸九曬法制首烏引起肝毒性的程度最輕。

Objective To explore the mechanism of hepatotoxicity of Radix Polygoni Multiflori Preparata based on network pharmacology and experimental verification. Methods The active components and action targets of Radix Polygoni Multiflori Preparata were collected by using the systematic pharmacology analysis platform of traditional Chinese medicine (TCMSP), and the integrated pharmacology research platform of traditional Chinese medicine (TCMIP). Liver injury related targets were obtained through Genecards and OMIM databases. After the common targets were screened by Venny diagram, PPI analysis was carried out by STRING database, the drug-component-target network was constructed by Cytoscape software, and GO enrichment analysis and KEGG pathway analysis were carried out by R language. Finally, the above results were further verified by in vivo experiments. Results 30 active components of Radix Polygoni Multiflori Preparata, and 527 hepatotoxicity related targets were obtained, and 48 common targets of Radix Polygoni Multiflori Preparata and liver injury were collected, including JUN, MAPK1, CYP3A4, etc. KEGG pathway analysis screened 135 related signal pathways, indicating that nonalcoholic fatty liver pathway and TNF signal pathway may play a key role in the hepatotoxicity of Radix Polygoni Multiflori Preparata. In vivo experiments showed that processed Radix Polygoni Multiflori could effectively reduce the hepatotoxicity of Radix Polygoni Multiflori, and the effect of processing of steamed for nine times and shined for nine times was the best. Conclusion Hepatotoxicity of Radix Polygoni Multiflori Preparata has the characteristics of multi-component, multi-target and multi-channel synergy, which provides a theoretical basis for the further study of the complex mechanism of hepatotoxicity of Radix Polygoni Multiflori.

R285.5

國家自然科學(xué)基金資助項目（81373988）；陜西省科技廳青年項目（2021JQ-728）