曾子修 申伟 魏竞竞 王敏 王莹 张昕洋 金香兰 张允岭

摘要 目的：采用網络药理学方法探讨健脾益肾化浊方治疗卒中后认知障碍（PSCI）的作用机制。方法：利用中药系统药理学数据库与分析平台（TCMSP）、中医药综合数据库（TCMID）及ETCM数据库筛选健脾益肾化浊方的活性成分，运用Swiss Target Prediction数据库对活性成分进行靶点预测;运用GeneCards数据库筛选PSCI相关疾病靶点;运用RStudio软件对健脾益肾化浊方及PSCI共同靶点绘制韦恩图;将二者共同靶点通过STRING及Metascape数据库分别进行PPI分析，基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析;运用Cytoscape 3.6.0绘制“健脾益肾化浊方-靶点-PSCI-通路”网络图;采用AutoDock对核心成分及核心靶点进行分子对接验证。结果：筛选出健脾益肾化浊方39种活性成分和553个靶点，筛选出PSCI潜在靶点2 305个，二者共同靶点为254个。通过GO及KEGG富集分析，发现健脾益肾化浊方可能通过突触可塑性、抗细胞凋亡、抗炎等多靶点、多途径发挥对PSCI的治疗作用。分子对接结果提示活性成分Stigmasterol与核心靶点（MAPK1、SRC、MAPK3、TP53、HSP90AA1），Palmatine与核心靶点（AKT1）具有较好的结合活性。结论：健脾益肾化浊方治疗PSCI可能通过调节突触可塑性、抗细胞凋亡、抗炎等生物学过程发挥作用。

关键词 健脾益肾化浊方;卒中后认知障碍;网络药理学;作用机制;中药;靶点;信号通路;分子对接

Mechanism of Jianpi Yishen Huazhuo Formula in Treatment of Post Stroke Cognitive Impairment Based on Network Pharmacology

ZENG Zixiu1，SHEN Wei2，WEI Jingjing1，WANG Min1，WANG Ying1，ZHANG Xinyang1，JIN Xianglan3，ZHANG Yunling2

（1 Graduate School of Beijing University of Chinese Medicine，Beijing 100029，China; 2 Xiyuan Hospital，China Academy of Chinese Medical Sciences，Beijing 100091，China; 3 Dongfang Hospital，Beijing University of Chinese Medicine，Beijing 100078，China）

Abstract Objective：To explore the mechanism of the Jianpi Yishen Huazhuo Prescription in treatment of post stroke cognitive impairment （PSCI） by using network pharmacology method.Methods：TCMSP，TCMID and ETCM databases were used to screen the active ingredients of the Jianpi Yishen Huazhuo Prescription，and the Swiss Target Prediction database was used to predict the target of the active ingredients.The GeneCards database was used to screen PSCI related disease targets.RStudio software was used to draw the Wien diagram for the common targets of the Jianpi Yishen Huazhuo Formula and PSCI.The PPI analysis，GO enrichment analysis and KEGG enrichment analysis were performed on the 2 common targets through the String and Metascape databases.Cytoscape 3.6.0 was used to draw the network diagram of the Jianpi Yishen Huazhuo Prescription-target point-PSCI-pathway.The AutoDock was used for molecular docking verification of core components and core targets.Results：A total of 39 active ingredients and 553 targets of the Jianpi Yishen Huazhuo Formula were screened out，and the 2305 potential targets of PSCI were screened out，among which the common targets were 254.Through the GO and KEGG enrichment analysis，it was found that the Jianpi Yishen Huazhuo Formula might play a therapeutic effect on PSCI through multiple targets and pathways such as synaptic plasticity，anti-apoptosis and anti-inflammation.The molecular docking results indicated that the active component Stigmasterol had good binding activity with the core target （MAPK1，Src，MAPK3，TP53，HSP90Aa1） and Palmatine had good binding activity with the core target （AKT1）.Conclusion：The Jianpi Yishen Huazhuo Formula may play an important role in the treatment of PSCI by regulating synaptic plasticity，anti-apoptosis and anti-inflammation.

Keywords Jianpi Yishen Huazhuo Formula; Post stroke cognitive impairment; Network pharmacology; Mechanism; Chinese medicinals; Target; Signaling pathway; Molecular docking

中图分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.23.009

卒中后认知障碍（Post Stroke Cognitive Impairment，PSCI）特指卒中后发生的认知功能下降，是血管性认知障碍（Vascular Cognitive Impairment，VCI）的一个重要亚型。基于我国的一项流调研究显示，PSCI的总体患病率高达80.97%，严重影响患者生命质量及生存时间[1]。……