目的 基于網(wǎng)絡(luò)藥理學(xué)與分子對接技術(shù)探討當(dāng)歸四逆湯治療系統(tǒng)性硬化癥的作用機(jī)制。方法 通過TCMSP數(shù)據(jù)庫檢索當(dāng)歸四逆湯中的活性成分并以Swiss Target Prediction數(shù)據(jù)庫預(yù)測各活性成分的靶點，采用GeneCards數(shù)據(jù)庫收集系統(tǒng)性硬化癥疾病靶點，取其中共同靶點作為潛在的作用靶點并導(dǎo)入String數(shù)據(jù)庫建立蛋白相互作用（PPI）網(wǎng)絡(luò)，以Cytoscape軟件進(jìn)行網(wǎng)絡(luò)拓?fù)浞治?。將PPI靶點導(dǎo)入DAVID數(shù)據(jù)庫進(jìn)行基因本體（GO）功能和京都基因組百科全書（KEGG）通路富集分析并以O(shè)micShare平臺將結(jié)果可視化。構(gòu)建“通路–靶點”網(wǎng)絡(luò)并篩選其中關(guān)鍵靶點，并采用CB-Dock平臺將作用靶點與活性成分進(jìn)行分子對接以篩選潛在藥效成分。結(jié)果 收集得到141個當(dāng)歸四逆湯活性成分及1 047個相關(guān)靶點，系統(tǒng)性硬化癥疾病靶點1 568個。篩選出潛在作用靶點266個，其中關(guān)鍵靶點6個，分別為蛋白激酶B1（Akt1）、血管內(nèi)皮生長因子受體2（KDR）、V-Ha-Ras肉瘤病毒癌基因同源物（HRAS）、促分裂原活化蛋白激酶1（MAPK1）、促分裂原活化蛋白激酶3（MAPK3）、血管內(nèi)皮生長因子A（VEGFA）。主要涉及MAPK信號通路、磷脂酰肌醇3-激酶（PI3K）/Akt信號通路、Rap1信號通路、黏著斑、脂質(zhì)和動脈粥樣硬化、流體剪切應(yīng)力和動脈粥樣硬化等通路的調(diào)節(jié)。分子對接結(jié)果顯示，水鬼蕉賓堿、芍藥苷、酸棗仁皂苷A等活性成分為治療中的潛在藥效成分。結(jié)論 當(dāng)歸四逆湯以多組分、多靶點、多通路干預(yù)系統(tǒng)性硬化癥，其機(jī)制涉及免疫、血管損傷和細(xì)胞外基質(zhì)合成等的調(diào)節(jié)。

Objective To explore the mechanism of Danggui Sini Decoction in treatment of systemic scleroderma based on network pharmacology and molecular docking method. Method Active substances of Danggui Sini Decoction and related targets were obtained from TCMSP database and Swiss Target Prediction database, the disease targets of systemic scleroderma were acquired from GeneCards database. The intersection targets were selected as potential active targets and import String database to construct PPI network. The network topology analysis was performed by Cytoscape software. The PPI targets were input DAVID database to perform GO and KEGG enrichment analysis and visualized by OmicShare platform. The “targets - pathway” network was construct to screening the key targets. CB-dock platform was utilized to perform the molecular docking between active targets and active substances to screen potential pharmacodynamic components. Results A total of 141 active substances and 1 047 related targets were acquired, and 1 568 diseases targets of systemic scleroderma were obtained. There were 266 potential active targets, including 6 key targets, namely Akt1, KDR, HRAS, MAPK1, MAPK3, and VEGFA. It’s mainly involving MAPK signaling pathway, PI3K/Akt signaling pathway, Rap1 signaling pathway, focal adhesion, lipid and atherosclerosis and fluid shear stress, and atherosclerosis. Molecular docking results showed that caribine, paeoniflorin, and jujuboside A were potential pharmacodynamic components. Conclusion Danggui Sini Decoction might intervene systemic scleroderma by multi- components, multi-targets, and multi-pathways, the mechanism involves the regulation of immunity, vascular injury, and extracellular matrix synthesis.

吉林省科技發(fā)展計劃項目（YDZJ202201ZYTS292）；吉林工程技術(shù)師范學(xué)院校級科研項目（BSKJ202002）