基于网络药理学和实验验证探究延胡索乙素治疗急性心肌缺血的作用机制

LIN Po-li; LIN Po-li; CAO Jun-ling; CAO Jun-ling; REN Ping; REN Ping; CHEN Jia-li; CHEN Jia-li; CAO Bo-ya; CAO Bo-ya; HE Ping; HE Ping; ZHENG Chang-hui; ZHENG Chang-hui; LI Qi-wen; LI Qi-wen; WANG Wei; WANG Wei; ZHANG Jian

doi:10.1007/s11655-023-3644-x

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基于网络药理学和实验验证探究延胡索乙素治疗急性心肌缺血的作用机制

Original Article | Updated：2023-11-21

- 基于网络药理学和实验验证探究延胡索乙素治疗急性心肌缺血的作用机制
- Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia
- 中国结合医学杂志（英文版） 2023年29卷第12期页码：1087-1098
- Affiliations：
  
  1.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing (100029), China
  2.Department of Pharmacy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing (100078), China
  3.School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing (100029), China
  4.School of Life Sciences, Beijing University of Chinese Medicine, Beijing (100029), China
  5.School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou (510006), China
  6.Beijing Key Laboratory of TCM Syndrome and Formula, Beijing (100029), China
  7.Key Laboratory of Beijing University of Chinese Medicine, Ministry of Education, Beijing (100029), China
- Author bio：
  
  Dr. ZHANG Jian, E-mail: zhangjian@bucm.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(82004095);the Fundamental Research Funds for the Central Universities(2021-JYB-XJSJJ031)
- DOI：10.1007/s11655-023-3644-x
  中图分类号：
- 纸质出版日期：2023-12，
  
  网络出版日期：2023-08-22，
  
  录用日期：2023-05-26
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基于网络药理学和实验验证探究延胡索乙素治疗急性心肌缺血的作用机制[J]. 中国结合医学杂志（英文版）, 2023,29(12):1087-1098.

LIN Po-li, LIN Po-li, CAO Jun-ling, et al. Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2023,29(12):1087-1098.
基于网络药理学和实验验证探究延胡索乙素治疗急性心肌缺血的作用机制[J]. 中国结合医学杂志（英文版）, 2023,29(12):1087-1098. DOI： 10.1007/s11655-023-3644-x.

LIN Po-li, LIN Po-li, CAO Jun-ling, et al. Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2023,29(12):1087-1098. DOI： 10.1007/s11655-023-3644-x.

摘要

目的

探索延胡索乙素 (tetrahydropalmatine

THP) 对急性心肌缺血 (acute myocardial ischemia

AMI) 的潜在分子机制.

方法

首先

从SymMap数据库、中药系统药理学数据库与分析平台以及Swiss Target Prediction数据库中对THP靶基因和AMI靶基因进行收集

获取THP和AMI之间的重叠基因

对其进行GO和KEGG富集分析并构建蛋白质相互作用网络. 接着

通过分子对接评估预测蛋白与THP之间的结合亲和力. 最后

基于AMI小鼠模型和H9C2心肌细胞氧糖剥夺 (oxygen and glucose deprivation

OGD) 模型从体内和体外两个水平探究THP对AMI的保护作用

并通过实时荧光定量 (RT-qPCR) 方法验证其对靶基因的调控作用.

结果

网络药理学结果显示

MMP9、PPARG、PTGS2、SLC6A4、ESR1、JAK2、GSK3B、NOS2和AR是THP治疗AMI潜在靶基因. KEGG富集分析结果显示

THP的潜在靶基因参与调控能量代谢、炎症和激素等途径. 动物实验结果显示

与模型组相比

THP能够改善AMI小鼠心功能

减轻心肌细胞损伤

显著降低AMI后MMP9、PTGS2、SLC6A4、GSK3B和ESR1的基因表达水平 (

0.05

0.01) . 细胞实验结果显示

与模型组相比

THP可以显著提高H9C2心肌细胞的存活率 (

0.05

0.01)

抑制OGD模型中PPARG、ESR1和AR的基因表达水平 (

0.05

0.01) .

结论

THP具有改善AMI心功能

减轻心肌损伤的作用

可能通过抑制炎症、改善能量代谢和激素调节发挥作用.

Abstract

Objective:

To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).

Methods:

First

the target genes of THP and AMI were collected from SymMap Database

Traditional Chinese Medicine Database and Analysis Platform

and Swiss Target Prediction

respectively. Then

the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally

the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR

in vivo

and

in vitro

Results:

MMP9

PPARG

PTGS2

SLC6A4

ESR1

JAK2

GSK3B

NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function

as well as alleviated myocardial cell damage. Furthermore

THP significantly decreased the RNA expression levels of MMP9

PTGS2

SLC6A4

GSK3B and ESR1 (

0.05

0.01) after AMI.

In vitro

THP significantly increased H9C2 cardiomyocyte viability (

0.05

0.01) and inhibited the RNA expression levels of PPARG

ESR1 and AR (

0.05

0.01) in OGD model.

Conclusions:

THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation

the improvement of energy metabolism and the regulation of hormones.

关键词

延胡索乙素急性心肌缺血炎症能量代谢激素

Keywords

tetrahydropalmatineacute myocardial infarctioninflammationenergy metabolismhormone

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