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基于网络药理学筛选黄芪香草酸对高血压性心脏重塑的保护作用研究

[Study on protective effect of vanillic acid from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology screen].

作者信息

Wang Bo-Yang, Liu Tian-Long, Liu Jing, Zhang Ming-Jie, Sun Jian-Jun, Liu Xiao-Lei, Ma Rui-Lian

机构信息

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.

出版信息

Zhongguo Zhong Yao Za Zhi. 2020 Jan;45(2):367-373. doi: 10.19540/j.cnki.cjcmm.20191022.402.

Abstract

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. Angiotensin Ⅱ(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 1 197 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.

摘要

基于网络药理学和心脏RNA测序数据,鉴定并验证黄芪对高血压性心脏重塑的活性成分。利用网络药理学建立黄芪单体及其干预靶点数据库。然后通过分析心脏RNA测序数据筛选与心脏重塑相关的基因。收集与心脏重塑相关的基因和黄芪成分靶点之间的重叠部分,以获得对高血压性心脏重塑具有保护作用的单体。采用血管紧张素Ⅱ(AngⅡ)诱导的小鼠心脏重塑模型,验证黄芪活性成分对高血压性心脏重塑的保护作用。最终,共81个单体和1197个靶点纳入我们的数据库。小鼠RNA测序数据显示,与空白组小鼠相比,心脏重塑小鼠心肌组织中983个基因显著上调,465个基因下调。通过心脏重塑相关基因与靶点的重叠发现92个基因,涉及59个黄芪单体。进一步研究发现,香草酸(VA)可干预27个与高血压性心脏重塑相关的基因,排名第一。同时,VA可显著抑制AngⅡ诱导的体内心脏重量与体重之比、心脏重量与胫骨长度之比、心肌组织中ANP和BNP mRNA水平、心肌组织损伤、心脏纤维化水平和心脏肥大水平的增加。这些结果表明,基于网络药理学筛选的VA对AngⅡ诱导的心脏重塑具有保护作用。

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