基于脑心同治理论探究生脉注射液治疗脑缺血再灌注损伤机制  

Study on the Mechanism of Shengmai Injection(生脉注射液)in the Treatment of Cerebral Ischemia-Reperfusion Injury Based on the Theory of Simultaneous Treatment of Heart and Brain

作　　者：齐大河 马桦 丁萌萌 王可欣 陈媛媛 孔令博[1] QI Dahe;MA Hua;DING Mengmeng;WANG Kexin;CHEN Yuanyuan;KONG Lingbo(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]南京中医药大学附属医院,江苏南京210029

出　　处：《辽宁中医药大学学报》2023年第6期28-37,共10页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1705001);北京中医药大学重点攻关项目(2020-JYB-ZDGG-110);北京中医药大学东直门医院科技创新项目(DZMKJCX-2022-006)。

摘　　要：目的 基于“脑心同治”理论和生脉注射液在心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的使用,创新性地使用网络药理学及分子对接技术初步探讨生脉注射液治疗脑缺血再灌注损伤的作用机制。方法 通过TCMSP、BATMAN-TCH、PubChem数据库并结合文献收集生脉注射液的有效成分及靶点信息,由GeneCards及OMIM数据库收集脑缺血再灌注损伤(cerebral ischemia reperfusion injury,CIRI)靶点,经过Uniprot校正基因名后取交集靶点,导入STRING数据库构建蛋白互作图及拓扑分析,运用Metascape数据库对蛋白质互作(protein-protein interaction,PPI)网络筛选的关键靶点进行基因本体(gene ontology,GO)及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析,利用AutoDock Tools软件进行分子对接验证。结果 生脉注射液治疗CIRI的主要活性成分为豆甾醇、人参炔三醇、β-谷甾醇、人参皂苷Rh2等,核心靶点主要为TNF、IL-6、IL-1β、EGFR、BDNF、Caspase3等,主要涉及PI3K-Akt、MAPK及Th17细胞分化信号通路,分子对接显示豆甾醇、β-谷甾醇及人参皂苷Rh2与核心靶点稳定结合。结论 该研究初步探究了生脉注射液治疗CIRI的作用机制,揭示生脉注射液可能是通过抑制再灌注过程中细胞凋亡、炎症反应及线粒体功能障碍等方面来发挥作用,后期将基于PI3K-Akt信号通路进行动物实验进一步验证生脉注射液的作用机制。Objective Based on the idea of“simultaneous treatment of heart and brain”and the use of Shengmai Injection(生脉注射液)in myocardial reperfusion injury,using network pharmacology and molecular docking technology to preliminarily explore the mechanism of Shengmai Injection in the treatment of cerebral ischemia reperfusion injury.Methods The effective components and target information of Shengmai Injection were collected through TCMSP,BATMAN-TCH database,PubChem database and literature.CIRI targets were collected through genecards and OMIM database.We will collect the intersection target information after UniProt corrected the gene name,and this information were input into the string database to analyze and build the protein interaction.Use metascape database to analyze go and KEGG for the key targets screened by PPI,screen the core action targets and related pathways.Using autodock tools software,the active ingredient and the core target were verified by molecular docking.Results The main active components of Shengmai Injection in the treatment of CIRI were stigmasterol,panaxytriol,β-sitosterol,ginsenoside Rh2,etc.the core targets were mainly TNF,IL-6,IL-1β,EGFR,BDNF,Caspase3,etc.,mainly involved in lipid and atherosclerosis pathway,MAPK signaling pathway,PI3K-Akt signaling pathway and Th17 cell differentiation pathway.Molecular docking results showed that stigmasterolβ-stable combination of sitosterol and ginsenoside Rh2 with core targets suggests that the mechanism of Shengmai Injection in the treatment of CIRI may be related to the inhibition of inflammatory response,apoptosis and mitochondrial dysfunction.Conclusion This study preliminarily explored the mechanism of action of Shengmai Injection in the treatment of CIRI,revealing that Shengmai Injection may play its role by inhibiting apoptosis,inflammatory reaction and mitochondrial dysfunction during reperfusion.Animal experiments based on PI3K Akt signaling pathway will be conducted in the future to further verify the mechanism of action of Shengm

关 键 词：生脉注射液 脑缺血再灌注损伤 脑心同治理论 网络药理学 分子对接 

分 类 号：R743.31[医药卫生—神经病学与精神病学]