目的運(yùn)用網(wǎng)絡(luò)藥理學(xué)結(jié)合分子對(duì)接技術(shù)探討蛇床子治療阿爾茨海默病的作用機(jī)制。方法 借助TCMSP數(shù)據(jù)庫(kù)獲取蛇床子的活性成分及潛在作用靶點(diǎn)；檢索GeneCards、OMIM、DisGeNET數(shù)據(jù)平臺(tái)得到阿爾茨海默病的潛在作用靶點(diǎn)，篩選兩者共同靶點(diǎn)；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(diǎn)，再借助R語言進(jìn)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(yùn)用AutoDock Vina軟件，對(duì)核心靶點(diǎn)和藥物主要活性成分進(jìn)行分子對(duì)接，驗(yàn)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(gè)，化學(xué)成分與疾病共同靶點(diǎn)56個(gè)，網(wǎng)絡(luò)拓?fù)浞治鲲@示B淋巴細(xì)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(diǎn)，通過調(diào)控神經(jīng)活性配體-受體的相互作用、鈣信號(hào)通路、p53信號(hào)通路、多種細(xì)胞凋亡、磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）信號(hào)通路、白細(xì)胞介素-17（IL-17）信號(hào)通路等發(fā)揮治療作用。分子對(duì)接驗(yàn)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?、蛇床子素與核心靶點(diǎn)GSK3B、PTGS2、Bcl-2的對(duì)接親合度較高。結(jié)論 蛇床子可通過多成分、多靶點(diǎn)和多通路的方式起到治療阿爾茨海默病的作用，為進(jìn)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(guó)家自然科學(xué)基金資助項(xiàng)目（82260904）；廣西自然科學(xué)基金重點(diǎn)項(xiàng)目（2019GXNSFDA245006）；廣西中醫(yī)腦病臨床研究中心項(xiàng)目（桂科AD20238028）；廣西高等學(xué)校高水平創(chuàng)新團(tuán)隊(duì)及卓越學(xué)者計(jì)劃（桂教人才202006）