基于网络药理学与实验验证方法探讨脑疏宁治疗脑梗死的分子机制  

Molecular mechanism of Naoshuning for cerebral infarction based on network pharmacology and experiment verification

作　　者：刘伟[1,3] 张梅奎[2] 宋发萍[1] LIU Wei;ZHANG Mei-kui;SONG Fa-ping(The First Clinical Medical College,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046;General Hospital of People’s Liberation Army,Beijing 100853;Hospital of Xi’an Petrolieum University,Xi’an 710065)

机构地区：[1]陕西中医药大学第一临床医学院,陕西咸阳712046 [2]中国人民解放军总医院,北京100853 [3]西安石油大学医院,西安710065

出　　处：《中南药学》2023年第3期692-700,共9页Central South Pharmacy

基　　金：北京市自然科学基金(No.7182156)。

摘　　要：目的基于网络药理学与实验验证方法探究脑疏宁治疗脑梗死的分子机制。方法利用网络药理学方法获取脑疏宁组方中药物活性成分、潜在靶点和脑梗死疾病相关靶点,并进行数据统计分析,利用GEO数据库、分子对接技术验证核心靶点;利用Zea-Longa线栓法建立Mcao脑缺血卒中大鼠模型进行动物实验验证。结果网络药理学分析发现,脑疏宁核心活性成分主要包括槲皮素、山柰酚、木犀草素、汉黄芩素、β-谷甾醇等,涉及核心靶点包括MMP9、HSP90AA1、COX2、RELA、PPARG等,可能通过PI3K-Akt信号通路、AGE-RAGE信号通路、IL-17信号通路、TNF信号通路、MAKP信号通路、NF-κB信号通路等发挥治疗脑梗死的作用;GEO数据库验证核心基因表明,对比正常组,脑梗死组13个基因表达具有显著差异(P<0.05);分子对接结果显示脑疏宁核心成分与脑梗死核心靶点具有很高的对接活性。动物实验显示脑疏宁可以改善大鼠缺血半暗带区组织的病理结构,通过下调其MMP9、COX2蛋白的表达治疗脑梗死。结论本研究从不同角度探究了脑疏宁治疗脑梗死的作用机制,并验证了脑疏宁可以通过多基因、多通路发挥抗脑梗死作用。Objective To determine the molecular mechanism of Naoshuning for cerebral infarction based on network pharmacology and experiment verification.Methods Network pharmacology was used to obtain the active ingredients,potential targets and cerebral infarction related targets in the Naosuning formula group,and the data were statistically analyzed.GEO database was used to verify the differential gene expression and molecular docking of the core targets.The cerebral infarction model of the middle cerebral artery embolization in rats was prepared by modified thread embolization method.Results The main active components for cerebral infarction included quercetin,kaempferol and luteolin.Totally 18 core genes for treating cerebral infarction,including MMP9,HSP90AA1,COX2,RELA,and PPARG were obtained.PI3K-Akt,AGE-RAGE,IL-17,TNF,MAKP,NF-κB signaling pathway and other core pathways were involved in the treatment of cerebral infarction.GEO database samples verified 13 core gene expression differences between the normal group and the cerebral infarction group.Molecular docking showed that the key active components of Naoshuning pre-scription group had high docking activity with the key gene targets of cerebral infarction.Naoshuning improved the pathological structure of the ischemic penumbra tissue in rats, and improved cerebral infarction by down-regulating the expression of MMP9 and COX2 proteins. Conclusion The mechanism of Naoshuning for cerebral infarction is explored from different angles. That Naoshuning has anti-cerebral infarction effect via multiple genes and multiple pathways is verified Swis­.

关 键 词：网络药理学 脑疏宁 脑梗死 实验验证 

分 类 号：R54[医药卫生—心血管疾病] R966[医药卫生—内科学]