摘要
该文旨在通过网络药理学和高血压心肌重构小鼠心肌转录测序数据在黄芪中筛选对高血压心肌重构具有保护作用的单体化合物并对其活性进行验证。利用网络药理学方法建立黄芪单体化合物及其干预靶点数据库;分析高血压心肌重构小鼠心肌转录组测序数据,筛选与高血压心肌重构发生有关的基因;两者取交集,得到对高血压心肌重构具有保护作用的单体化合物;利用血管紧张素Ⅱ(AngⅡ)微渗透泵构建高血压心肌重构小鼠模型并使用筛选的目标化合物进行干预以评价其活性。最终,81种黄芪单体化合物及其1197个干预靶点被纳入到数据库中;与空白组小鼠比较,高血压心肌重构小鼠心肌组织中分别有983个基因和465个基因表达水平较空白组小鼠显著上调和下调;在1197个黄芪干预靶点和1448个高血压心肌重构相关基因之间取交集,共有92个重叠基因,涉及59种黄芪单体化合物,其中,黄芪香草酸(vanillic acid,VA)能够干预27个与高血压心肌重构发生有关的基因,位居榜首。动物水平研究结果显示,VA对AngⅡ诱导的小鼠心体比和心胫比的增加、ANP和BNP在心肌组织中的表达、心肌组织损伤、纤维化、心肌肥厚具有显著的抑制作用。上述结果说明,基于网络药理学筛选的黄芪VA对AngⅡ诱导的高血压心肌重构具有一定的保护作用。
To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data.The monomers of A.membranaceus and their intervention target database were established by using network pharmacology.The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data.An overlap between genes related to cardiac remodeling and targets of ingredients form A.membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling.AngiotensinⅡ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A.membranaceus on hypertensive cardiac remodeling.Finally,a total of 81 monomers and 1197 targets were enrolled in our database.Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice,respectively.Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets,involving 59 monomers from A.membranaceus.Further research found that vanillic acid(VA)could intervene 27 genes associated with hypertensive cardiac remodeling,ranking top 1.Meanwhile,VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length,ANP and BNP mRNA levels in myocardial tissues,myocardial tissue damage,cardiac fibrosis level and cardiac hypertrophy level in vivo.Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.
作者
王伯阳
刘天龙
刘晶
张铭杰
孙建军
刘小雷
马瑞莲
WANG Bo-yang;LIU Tian-long;LIU Jing;ZHANG Ming-jie;SUN Jian-jun;LIU Xiao-lei;MA Rui-lian(Orthopaedic District B,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010030,China;Pharmacy Department,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010030,China;Pharmacology Department,Inner Mongolia Medical University,Hohhot 010110,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第2期367-373,共7页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(80960048)
内蒙古自治区自然科学基金项目(2019BS08003)
内蒙古医科大学百万工程项目[YKD2018KJBW(LH)0026].
关键词
黄芪
网络药理学
香草酸
心肌重构
保护作用
Astragalus membranaceus
network pharmacology
vanillic acid
cardiac remodeling
protective effect
作者简介
王伯阳,硕士研究生,住院医师,E-mail:328337997@qq.com;通信作者:马瑞莲,主任药师,研究方向为心血管药理学和临床药学,E-mail:maruilian001@163.com;通信作者:刘天龙,博士研究生,E-mail:tianlongliu1984@163.com
