目的運用網(wǎng)絡(luò)藥理學(xué)結(jié)合分子對接技術(shù)探討蛇床子治療阿爾茨海默病的作用機制。方法 借助TCMSP數(shù)據(jù)庫獲取蛇床子的活性成分及潛在作用靶點；檢索GeneCards、OMIM、DisGeNET數(shù)據(jù)平臺得到阿爾茨海默病的潛在作用靶點，篩選兩者共同靶點；應(yīng)用Cytoscape 3.7.1構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)圖并篩選發(fā)揮治療作用的關(guān)鍵靶點，再借助R語言進行基因本體（GO）功能分析、京都基因與基因組百科全書（KEGG）通路富集分析；運用AutoDock Vina軟件，對核心靶點和藥物主要活性成分進行分子對接，驗證網(wǎng)絡(luò)分析結(jié)果。結(jié)果 蛇床子包含主要活性成分20個，化學(xué)成分與疾病共同靶點56個，網(wǎng)絡(luò)拓撲分析顯示B淋巴細胞瘤-2（Bcl-2）、雌激素受體α（ESR1）、前列腺素內(nèi)過氧化物合酶2（PTGS2）、糖原合成酶激酶3β（GSK3B）、半胱氨酸蛋白水解酶3（CASP3）為關(guān)鍵靶點，通過調(diào)控神經(jīng)活性配體-受體的相互作用、鈣信號通路、p53信號通路、多種細胞凋亡、磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）信號通路、白細胞介素-17（IL-17）信號通路等發(fā)揮治療作用。分子對接驗證中受體與配體之間的結(jié)合能均≤−5.0 kcal/mol，結(jié)合性良好，其中O-乙酰二氫歐山芹酯、鄰-異戊?；渖角鄞肌⑸叽沧铀嘏c核心靶點GSK3B、PTGS2、Bcl-2的對接親合度較高。結(jié)論 蛇床子可通過多成分、多靶點和多通路的方式起到治療阿爾茨海默病的作用，為進一步探究蛇床子治療阿爾茨海默病的理論研究提供參考。

Objective To explore the mechanism of Cnidii Fructus in treatment of Alzheimer's disease by means of network pharmacology and molecular docking technique. Methods To obtain the active components and potential targets of Cnidii Fructus through TCMSP database. GeneCards, OMIM, and DisGeNET data platforms were searched to obtain the potential targets of Alzheimer's disease and screen the common targets of both. The protein interaction network map was constructed by Cytoscape3.7.1, and the key therapeutic targets were screened. Enrichment of GO and KEGG pathway was analyzed with R language. AutoDock Vina software was used to dock the core targets and the main active components of the drug to verify the results of network analysis. Results Cnidii Fructus contains 20 main active components, with 56 chemical components sharing common targets with the disease. Network topology analysis shows that Bcl-2, ESR1, PTGS2, GSK3B, and CASP3 may be the key targets for treatment. The therapeutic effect is mainly through the regulation of neuroactive ligand receptor interaction, calcium signaling pathway, p53 signaling pathway, multiple species of apoptosis, PI3K/Akt signaling pathway, IL-17 signaling pathway and so on. Molecular docking verification showed that O-acetylcolumbianetin, O-isovalerylcolum bianetin, and osthol have a high affinity in docking with core targets GSK3B, PTGS2, and Bcl-2. Conclusion Cnidii Fructus can treat Alzheimer's disease through a multi-component, multi-target, and multi-pathway approach, providing a reference for further theoretical research into the treatment of Alzheimer's disease with Cnidii Fructus.

R285;R971

國家自然科學(xué)基金資助項目（82260904）；廣西自然科學(xué)基金重點項目（2019GXNSFDA245006）；廣西中醫(yī)腦病臨床研究中心項目（桂科AD20238028）；廣西高等學(xué)校高水平創(chuàng)新團隊及卓越學(xué)者計劃（桂教人才202006）