目的 通過(guò)網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接技術(shù)探究川楝子肝毒性機(jī)制。方法 通過(guò)TCMSP、PubChem、SwissADME數(shù)據(jù)庫(kù)及文獻(xiàn)檢索篩選川楝子的潛在毒性成分，利用SwissTargetPrediction數(shù)據(jù)庫(kù)預(yù)測(cè)潛在毒性成分的作用靶點(diǎn)，再通過(guò)GeneCards數(shù)據(jù)庫(kù)搜索與肝臟損傷相關(guān)的靶點(diǎn)，將毒性成分預(yù)測(cè)靶點(diǎn)與肝臟損傷靶點(diǎn)取交集靶點(diǎn)，獲得毒性成分肝臟潛在作用靶點(diǎn)，再利用軟件Cytoscape 3.8.2版進(jìn)行毒性成分–預(yù)測(cè)靶點(diǎn)、毒性成分–潛在作用靶點(diǎn)、蛋白相互作用（PPI）網(wǎng)絡(luò)、毒性成分–潛在作用靶點(diǎn)–核心通路網(wǎng)絡(luò)的構(gòu)建，采用AutoDock 1.5.6版進(jìn)行分子對(duì)接，并應(yīng)用PyMOL軟件對(duì)對(duì)接結(jié)果進(jìn)行可視化示例。結(jié)果 篩選得到6個(gè)川楝子潛在毒性化合物，分別是toosandanin、meliasenin B、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal、butenolide、5-hydxoymethylfurfural，與肝臟損傷共同作用靶點(diǎn)103個(gè)。GO和KEGG結(jié)果顯示，川楝子通過(guò)蛋白質(zhì)磷酸化、凋亡過(guò)程的負(fù)調(diào)控、對(duì)異種生物刺激的反應(yīng)、酶激活的正向調(diào)控等過(guò)程引起肝臟毒性。分子對(duì)接結(jié)果顯示，川楝子中toosandanin、trichilinin D、1-O-tigloy-1-O-debenzoylohchinal與關(guān)鍵靶點(diǎn)具有較好的結(jié)合能力。結(jié)論 應(yīng)用網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接技術(shù)對(duì)川楝子致肝毒成分、機(jī)制、靶點(diǎn)、通路進(jìn)行了初步探索，為進(jìn)一步對(duì)川楝子的臨床應(yīng)用研究和效應(yīng)機(jī)制提供數(shù)據(jù)支持。

Objective To investigate the mechanism of hepatotoxicity of Toosendan Fructus by network pharmacology and molecular docking technique. Methods The potential toxic components of Toosendan Fructus were screened through TCMSP, PubChem, SwissADME databases, and literature search, the targets of potential toxic components were predicted using SwissTargetPrediction database, and then the targets related to liver injury were searched through GeneCards database, and the intersecting targets between the predicted targets of the toxic components and liver injury targets were taken to obtain the potential targets of action of the toxic components in the liver. The intersection target was taken to obtain the liver potential action target of toxic ingredients, and then the software Cytoscape version 3.8.2 was used for the construction of toxic ingredient-predicted target, toxic ingredient-potential action target, PPI network, and toxic ingredient-potential action target-core pathway network, and the molecular docking was carried out by using the version of AutoDock 1.5.6 and the open source software PyMOL was applied to visualize the docking results. The docking results were visualized as examples. Results Six potentially toxic compounds of Toosendan Fructus, namely toosandanin, meliasenin B, trichilinin D, 1-O-tigloy-1-O-debenzoylohchinal, butenolide, and 5-hydxoymethylfurfural were screened for liver damage with common targets of action 103. GO and KEGG results showed that Toosendan Fructus induced hepatotoxicity through processes such as protein phosphorylation, negative regulation of apoptotic processes, response to xenobiotic stimuli, and positive regulation of enzyme activation. Molecular docking results showed that three potentially toxic components of Toosendan Fructus, toosandanin, trichilinin D, and 1-O-tigloy-1-O-debenzoylohchinal, had good binding capacity to the key targets. Conclusion The preliminary exploration of hepatotoxic components, mechanisms, targets, and pathways of Toosendan Fructus was carried out by applying network pharmacology and molecular docking techniques to provide data support for further clinical application studies and effect mechanisms of Toosendan Fructus.

R285

遵義醫(yī)科大學(xué)未來(lái)“醫(yī)技名匠”人才培養(yǎng)計(jì)劃（遵醫(yī)未來(lái)醫(yī)技名匠[2022]03）