目的 利用網(wǎng)絡藥理學、分子對接技術，篩選并分析丹參治療缺血性腦卒中（CIS）的關鍵化合物、作用靶點、生物學功能及信號通路，闡述其可能的作用機制。方法 使用TCMSP數(shù)據(jù)庫檢索丹參的活性成分及作用靶點，在GeneCards、NCBI和OMIM數(shù)據(jù)庫中獲取CIS的靶點，并將藥物和疾病交集后的靶點輸入STRING數(shù)據(jù)庫，構建蛋白質相互作用網(wǎng)絡，利用Cytoscape 3.7.2軟件構建藥物-化合物-作用靶點-疾病網(wǎng)絡。通過Bioconductor進行GO功能富集和KEGG通路分析。采用AutoDock Tools 1.5.6、AutoDock vina 1.1.2將得到的關鍵活性成分和核心靶點進行分子對接，運用Pymol和Ligplot軟件對結果進行可視化。結果 從丹參中共篩選出65個活性成分和108個對應靶點，以及CIS交集后獲得靶點87個，其中度值大于50的靶點有6個，包括AKT1、IL6、FOS、VEGFA、MAPK1、EGFR，即本研究的核心靶點。GO功能富集分析得到GO條目124個（P<0.05），KEGG通路富集分析篩出134條信號通路（P<0.05），以PI3K-AKT信號通路所占靶點數(shù)目最多。構建的藥物-化合物-作用靶點-疾病網(wǎng)絡顯示，木犀草素、丹參酮Ⅱ_A等活性化合物在整個網(wǎng)絡中發(fā)揮著關鍵作用；分子對接結果顯示，木犀草素、丹參酮Ⅱ_A與6個核心靶蛋白均具有較好的親和力（結合能遠小于-5 kJ/mol）。結論 丹參的主要活性化合物，包括木犀草素、丹參酮Ⅱ_A等，可作用于AKT1、IL6、FOS、VEGFA、MAPK1、EGFR等核心靶點，共同參與調節(jié)PI3K-AKT等多條信號通路，發(fā)揮抑制細胞凋亡、抗炎、神經(jīng)保護等作用，可能是丹參治療CIS的潛在機制。

Objective To screen the key compounds, targets, biological functions and signal pathways of Salviae miltiorrhizae in treatment of cerebral ischemic stroke by using network pharmacology and molecular docking techniques, and to analyze the possible mechanism of action. Methods TCMSP database was emaployed to search for the active ingredients and targets of Salviae miltiorrhizae, as well as the targets of CIS were obtained in GeneCards, NCBI and OMIM database. Then drug targets and disease targets were overlapped, and put into STRING database to establish a protein interaction network. Moreover, drug-compound-targetdisease network was constructed and GO function and KEGG pathway enrichment analysis were carried out in Bioconductor. With the aid of AutoDock Tools 1.5.6 and AutoDock vina 1.1.2, the key active ingredients and core targets were docked at molecular level, and the results were visualized by using Pymol and Ligplot software. Results A total of 65 active ingredients and 108 targets were selected out from Salviae miltiorrhizae, and 2 558 targets were collected related to CIS. After intersection, 87 targets were obtained, among which the degree value of 6 targets was greater than 50, including AKT1, IL6, FOS, VEGFA, MAPK1, EGFR, as the core targets of this study. A total of 124 GO entries and 134 signal pathways were identified, with the PI3K/AKT signal pathway occupying the largest number of targets. The results showed that luteolin and tanshinone Ⅱ_A played a key role in the drug-compoundtarget-disease network and well connected to six core targets (binding energy is much less than -5 kJ/mol). Conclusion The main active compounds of Salviae miltiorrhizae, such as luteolin, tanshinone Ⅱ_A, could target for AKT1, IL6, FOS, VEGFA, MAPK1, EGFR, and participated in the regulation of PI3K/AKT signaling pathway and many other pathways, responsible for anti-apoptosis, antiinflammatory, neuroprotection and other biological functions, that may be potential mechanisms of Salvia miltiorrhiza in treatment of CIS.

R284.3

北京市雙一流高層次人才科研經(jīng)費項目（1000041510053）