Study on the mechanism of <italic style="font-style: italic">Suxiao Jiuxin</italic> Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics

YUAN Mengfei; SHEN Xiaoxu; WENG Jieqiong; ZHANG Jingfang; SHEN Xingchen; WENG Yayi

doi:10.3969/j.issn.1006-2157.2023.11.011

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Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics

Clinical Studies | 更新时间：2023-12-08

- Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 11, Pages: 1561-1573(2023)
- 作者机构：
  
  北京中医药大学东直门医院心血管内科　北京　100700
- 作者简介：
  
  Prof.SHEN Xiaoxu, Ph.D., Chief Physician, Doctoral Supervisor. Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5, Haiyuncang, Dongcheng District, Beijing 100700. E-mail: shenxiaoxupaper@sina.com
- 基金信息：
  
  National Key R&D Program of China(DZMKJCX-2023-030)
- DOI：10.3969/j.issn.1006-2157.2023.11.011
  CLC： R259.414
- Received：19 April 2023，
  
  Online First：26 October 2023，
  
  Published：30 November 2023
- 稿件说明：
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YUAN Mengfei, SHEN Xiaoxu, WENG Jieqiong, et al. Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(11): 1561-1573. DOI: 10.3969/j.issn.1006-2157.2023.11.011.
DOI：

YUAN Mengfei, SHEN Xiaoxu, WENG Jieqiong, et al. Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(11): 1561-1573. DOI: 10.3969/j.issn.1006-2157.2023.11.011. DOI：

摘要

目的

鉴定速效救心丸干预稳定型心绞痛气滞血瘀证患者的差异代谢物、代谢通路，探讨速效救心丸相关治疗作用机制。

方法

选择2019年9月—2021年9月在东直门医院等接受义诊的患者和健康人，试验组纳入30例稳定型心绞痛气滞血瘀证患者，对照组纳入30名健康人。利用液相色谱-质谱技术对两组受试者进行血清代谢组学分析，采用多变量偏最小二乘回归分析模型的前2个主成分的VIP值，结合单变量分析差异倍数和

值筛选差异代谢物，基于京都基因与基因组百科全书数据库对差异代谢物进行代谢通路富集分析。

结果

共鉴定出试验组与对照组的差异代谢物18种，其中，4-羟基肉桂酰亚胺、胆绿素-Ⅸ-β、2-亚甲基谷氨酸等代谢物含量低于健康人，左旋肉碱、维生素BT、胍丁胺、柠康酸、鸟嘌呤、薄荷脑等代谢物含量高于健康人。对比试验组患者服用速效救心丸治疗前后的21种差异代谢物，治疗后细菌叶绿素a、植物鞘氨醇、4-氧视黄醇、神经酰胺、1-甲基鸟嘌呤等代谢物含量较治疗前下降，6-酮前列腺素E1、树脂毒素、前列腺素G2含量较治疗前升高。差异代谢物质的异常变化提示稳定型心绞痛患者体内可能存在氨基酸、脂质、视黄醇、嘌呤、卟啉和叶绿素、瞬时受体电位通道的炎症介质调节、血清素能突触等多种代谢途径的紊乱。

结论

稳定型心绞痛气滞血瘀证患者与健康人体内代谢物存在明显差异，速效救心丸具有双向调节体内血清代谢物的作用，从而发挥调节肠道菌群、维持肠道屏障、改善血脂水平、增加血管内皮功能的稳定、减轻组织细胞炎症反应、抗氧化等作用。

Abstract

Objective

To identify changes in metabolites in patients with stable angina pectoris(SAP) with qi stagnation and blood stasis

explore the differential metabolites and metabolic pathways associated with SAP

and determine the therapeutic mechanisms associated with

Suxiao Jiuxin

Pills.

Methods

Patients and healthy recruited from September 2019 to September 2021 in Dongzhimen Hospital and other departments. The experimental group included 30 SAP patients with qi stagnation and blood stasis

and the control group included 30 healthy individuals. Serum metabolomics analysis was performed on both groups using liquid chromatography/mass spectrometry (LC/MS)

and the VIP values of the first two principal components of the multivariate partial least squares-discriminant analysis model combined with a univariate analysis of difference fold-change and

values were used to screen differentially expressed metabolites. Metabolic pathway enrichment analysis of differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes database.

Results

A total of 18 significant differential metabolites were identified in the experimental and control groups; the levels of 4-hydroxycinnamimide

biliverdin-Ⅸ-β

and 2-methylene glutamic acid were lower in SAP patients than in healthy individuals

and the L-carnitine

vitamin BT

agmatine

citraconic acid

guanine

and menthol levels were higher. Twenty-one significant differential metabolites were identified in the experimental group before and after the administration of

Suxiao Jiuxin

Pills. The levels of bacterial chlorophyll-a

sphingosine

4-oxoretinol

ceramide

1-methylguanine

and other metabolites decreased after administration

while those of 6-ketoprostaglandin E1

resin toxin

and prostaglandin G2 increased. The abnormal changes in differential metabolites suggest that numerous metabolic pathways are disordered in SAP patients

including amino acids

lipids

retinol

purines

porphyrins

chlorophyll

inflammatory mediator regulation of transient receptor potential channels

and serotonergic synapses.

Conclusion

There are significant differences in metabolites between patients with SAP with qi stagnation and blood stasis and healthy people

and

Suxiao Jiuxin

Pills have positive and negative effects on regulating serum metabolites

in vivo

thus regulating intestinal flora

maintaining the normal intestinal barrier

improving blood lipid levels

increasing the stability of vascular endothelial function

reducing tissue cell inflammation response

and inducing antioxidant effects.

关键词

Keywords

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Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics

DOI：10.3969/j.issn.1006-2157.2023.11.011

摘要

Abstract

关键词

Keywords

references