目的 運用網(wǎng)絡藥理學和分子對接技術挖掘梔子對缺血性腦卒中和出血性腦卒中的共同干預機制，明確解毒中藥治療缺血性腦卒中和出血性腦卒中的共性靶點與關鍵通路。方法 通過檢索中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）、中醫(yī)百科全書（ETCM）、中藥分子機制的生物信息學分析工具（BATMAN-TCM）以及中醫(yī)藥綜合數(shù)據(jù)庫（TCMID）收集梔子的活性成分，運用TCMSP、STTICH、Swiss數(shù)據(jù)庫進行靶點預測，從在線人類孟德爾遺傳數(shù)據(jù)庫（OMIM）、GeneCard數(shù)據(jù)庫、DisGeNET數(shù)據(jù)庫、TTD疾病數(shù)據(jù)庫搜集缺血性腦卒中和出血性腦卒中的疾病靶點，將2者取交集得到的靶標導入STRING平臺進行蛋白質(zhì)相互作用（PPI）網(wǎng)絡分析，運用Cytoscape軟件進行網(wǎng)絡拓撲分析，同時運用DAVID軟件對交集靶標進行基因本體論（GO）富集分析和京都基因組百科全書（KEGG）通路分析，最后利用分子對接技術驗證梔子有效成分與核心靶點的結合作用。結果 從梔子中共篩選出68個活性成分，包括山柰酚、芹菜素、槲皮素、熊果酸、京尼平苷、梔子苷等，梔子活性化合物與缺血性腦卒中和出血性腦卒中相關的治療靶點有205個，主要包括IL6、AKT1、INS、IL1B、VEGFA、TP53、MAPK3、CASP3、JUN、EGFR、MMP9等。分子對接顯示梔子的有效成分芹菜素、槲皮素、山柰酚、熊果酸等與IL6、AKT1、IL1B、TP53、MAPK3、CASP3、MMP9具有良好的結合能力。梔子主要通過調(diào)節(jié)腫瘤壞死因子（TNF）、低氧誘導因子-1（HIF-1）、（叉頭框蛋白） FoxO、磷脂酰肌醇-3激酶/蛋白激酶（PI3K-Akt）等信號通路發(fā)揮缺血性腦卒中和出血性腦卒中共性干預的作用。結論 梔子對缺血性腦卒中和出血性腦卒中的共性干預主要通過抑制免疫炎癥反應、調(diào)控細胞凋亡等過程發(fā)揮治療作用。

Objective To explore the common intervention mechanism of Gardeniae Fructus on ischemic stroke and hemorrhagic stroke by using network pharmacology and molecular docking technology, and to explore the common targets and key pathways of detoxifying Chinese medicine in treating ischemic stroke and hemorrhagic stroke.Methods The active components of Gardeniae Fructus were collected by searching the databases TCMSP, ETCM, BATMAN-TCM, and TCMID.The Online Mendelian inheritance in man(OMIM) database, Gene Card database, DisGeNET database and TTD database were used to collect the disease targets of ischemic stroke and hemorrhagic stroke.The targets obtained from the intersection of the Gardeniae Fructus and the diseases were imported into STRING platform for protein-protein interaction(PPI) network analysis.Cytoscape software was used for network topology analysis, and David software was used for Gene Ontology(GO) enrichment analysis and Kyoto encyclopedia of genomes(KEGG) pathway analysis of intersection targets.Finally, molecular docking technology was used to verify the binding effect of effective components of Gardeniae Fructus with core targets.Results A total of 68 active components were screened from Gardeniae Fructus including kaempferol, apigenin, quercetin, ursolic acid, genipin and so on.There were 205 therapeutic targets of the active compounds of Gardeniae Fructus related to ischemic stroke and hemorrhagic stroke including IL6, AKT1、INS, IL1 B, VEGFA, TP53, MAPK3, CASP3, JUN, EGFR and so on.Molecular docking showed that the effective components of Gardeniae Fructus, such as apigenin, quercetin, kaempferol and ursolic acid, had good binding ability with IL6, AKT1, IL1 B, TP53, MAPK3, CASP3 and MMP9.Gardeniae Fructus mainly played the role of common intervention on ischemic stroke and hemorrhagic stroke by regulating TNF signal pathway, HIF-1 signal pathway, FoxO signal pathway, PI3 K-Akt signal pathway and so on.Conclusion The common mechanisms of Gardeniae Fructus on ischemic stroke and hemorrhagic stroke mainly involve in inhibiting immune inflammatory response and regulating cell apoptosis.

R285.5

北京中醫(yī)藥大學中央高?；究蒲袠I(yè)務費項目（2019-JYB-JS-034）；北京中醫(yī)藥腦血管病防治辦公室建設項目（YW083）；國家衛(wèi)生健康委員會2019年重大疑難疾病中西醫(yī)臨床協(xié)作能力建設項目-腦梗死（YW082）