目的 基于網(wǎng)絡(luò)藥理學(xué)和分子模擬對接技術(shù)探究蘇合香丸治療缺血性卒中的活性成分和作用機制。方法 通過中藥系統(tǒng)藥理學(xué)平臺（TCMSP）和中醫(yī)藥綜合數(shù)據(jù)庫（TCMID）獲取蘇合香丸中15味藥材的化學(xué)成分和作用靶點，并通過PubChem數(shù)據(jù)庫和String平臺進行靶點預(yù)測和收集，采用GeneCards和DisGeNET數(shù)據(jù)庫獲得缺血性卒中相關(guān)基因，兩者取交集獲得共有靶點，并經(jīng)Cytoscape軟件將結(jié)果可視化，通過網(wǎng)絡(luò)拓撲算法獲得核心化合物和核心靶點；通過String平臺構(gòu)建PPI網(wǎng)絡(luò)獲得蘇合香丸治療缺血性卒中的重要靶點，通過DAVID平臺對重要靶點進行基因本體（gene ontology，GO）功能及京都基因與基因組百科全書（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析；使用Autodock Vina軟件進行分子對接，驗證網(wǎng)絡(luò)分析結(jié)果。結(jié)果 蘇合香丸的主要活性化合物66個，其中1，2，15，16-四氫丹參酮、蓽茇壬二烯哌啶、去甲波爾定、烏藥醚內(nèi)酯等9個化合物可能是蘇合香丸治療缺血性卒中的核心成分；篩選出蘇合香丸治療缺血性卒中的重要靶點63個，核心靶點11個，其中IL10、ESR1、CXCL8以及CASP3是關(guān)鍵的核心靶點；GO功能富集分析和KEGG通路富集分析顯示蘇合香丸主要對機體炎癥反應(yīng)、NO生成、平滑肌細胞增殖、細胞凋亡以及機體對脂多糖、藥物的細胞反應(yīng)等生物過程進行調(diào)控，并且可能通過調(diào)控TNF信號通路、Toll樣受體信號通路、HIF-1信號通路、PI3K-Akt信號通路、MAPK信號通路、FoxO信號通路以及神經(jīng)營養(yǎng)因子信號通路等途徑作用于缺血性卒中。結(jié)論 初步探究蘇合香丸治療缺血性卒中的潛在活性成分和可能的作用機制，為進一步闡明蘇合香丸治療缺血性卒中的藥效物質(zhì)、后期的深入開發(fā)研究提供了參考。

Objective To explore the active ingredients and mechanism of Suhexiang Pill in the treatment of ischemic stroke based on network pharmacology and molecular docking. Methods Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database(TCMID)were applied to obtain chemical components and potential targets of fifteen herbs in Suhexiang Pilll. The predicted targets of active compounds were collected from Pubchem database and STRING platform, Disease targets relating to ischemic stroke were screened out through GeneCards database and DisGeNET database, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Suhexiang Pill in treating ischemic stroke, Cytoscape software was used to construct the network of active ingredient-potential target genes, the key ingredients and core targets were selected based on topological parameters. A protein-protein interaction (PPI) network was constructed through the STRING platform and the core targets in the network were predicted, and the enrichment analyses of core targets were completed by DAVID database. Furthermore, a molecular docking method was used to verify the binding of the components with the main core targets using softwares such as Autodock Vina. Results There were 66 major active compounds in Suhexiang Pill, nine active compounds such as trijuganone B, pipernonaline, norboldine and linderane may be the main therapeutic ischemic stroke of Suhexiang Pill active ingredients. There were 63 core targets and 11 key targets in the treatment of ischemic stroke were obtained, IL10、ESR1、CXCL8 and CASP3 may be the main core targets of Suhexiang Pill in treating ischemic stroke. The results of GO enrichment analysis showed that the biological functions were mainly involved in the regulation of inflammatory response, nitric oxide biosynthetic process, smooth muscle cell proliferation, apoptosis process, response to lipopolysaccharide and response to drug. The results of KEGG pathway enrichment analysis showed that TNF signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway and Neurotrophin signaling pathway might be the key signaling pathways of Suhexiang Pill in treating ischemic stroke. Conclusion It is preliminarily explored the potential active ingredients and possible mechanisms of Suhexiang Pill in treatment of ischemic stroke, and provides reference for further elucidation of the pharmacological effects of Suhexiang Pill against ischemic stroke, subsequent development research.

R285.5

國家自然科學(xué)青年基金項目（81703870）