基于代谢组学探讨速效救心丸治疗稳定型心绞痛气滞血瘀证的作用机制

原梦飞; 沈晓旭; 翁洁琼; 张晶芳; 沈星辰; 翁雅逸

doi:10.3969/j.issn.1006-2157.2023.11.011

您当前的位置：

首页 >

文章列表页 >

基于代谢组学探讨速效救心丸治疗稳定型心绞痛气滞血瘀证的作用机制

临床研究 | 更新时间：2023-12-08

- 基于代谢组学探讨速效救心丸治疗稳定型心绞痛气滞血瘀证的作用机制
- Study on the mechanism of Suxiao Jiuxin Pills in treating stable angina pectoris with qi stagnation and blood stasis based on metabonomics
- 北京中医药大学学报 2023年46卷第11期页码：1561-1573
- 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：
  
  原梦飞，男，在读博士生
  # 沈晓旭，男，博士，教授，主任医师，博士生导师，主要研究方向：中西医结合防治心血管疾病，E-mail：shenxiaoxupaper@sina.com
- 基金信息：
  
  北京中医药大学东直门医院2023科技创新项目(DZMKJCX-2023-030);国家重点研发计划项目(2017YFC1700206)
- DOI：10.3969/j.issn.1006-2157.2023.11.011
  中图分类号： R259.414
- 纸质出版日期：2023-11-30，
  
  网络出版日期：2023-10-26，
  
  收稿日期：2023-04-19，
- 稿件说明：
移动端阅览
原梦飞, 沈晓旭, 翁洁琼, 等. 基于代谢组学探讨速效救心丸治疗稳定型心绞痛气滞血瘀证的作用机制[J]. 北京中医药大学学报, 2023,46(11):1561-1573.

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.
原梦飞, 沈晓旭, 翁洁琼, 等. 基于代谢组学探讨速效救心丸治疗稳定型心绞痛气滞血瘀证的作用机制[J]. 北京中医药大学学报, 2023,46(11):1561-1573. DOI： 10.3969/j.issn.1006-2157.2023.11.011.

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.

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

速效救心丸稳定型心绞痛气滞血瘀代谢组学液相色谱-质谱

Keywords

Suxiao Jiuxin Pillsstable angina pectorisqi stagnation and blood stasismetabolomicsliquid chromatography/mass spectrometry (LC/MS)

references

马丽媛，王增武，樊静，等. 《中国心血管健康与疾病报告2021》概要[J]. 中国介入心脏病学杂志，2022, 30(7)：481-496.

JU L, WEN Y, YIN J, et al. Metabonomic study of the effects of different acupuncture directions on therapeutic efficacy[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2016, 1009/1010: 87-95.

中华医学会心血管病学分会介入心脏病学组，中华医学会心血管病学分会动脉粥样硬化与冠心病学组，中国医师协会心血管内科医师分会血栓防治专业委员会，等．稳定性冠心病诊断与治疗指南[J].中华心血管病杂志，2018，46(9)：680-694.

中华中医药学会心血管病分会．冠心病心绞痛证候要素诊断标准[J].中医杂志，2018，59(6)：539-540.

朱文锋．证素辨证学[M].北京：人民卫生出版社，2008：8-319.

DUNN WB, BROADHURST D, BEGLEY P, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry[J]. Nat Protoc, 2011, 6(7)：1060-1083.

WEN B, MEI ZL, ZENG CW, et al. metaX: a flexible and comprehensive software for processing metabolomics data[J/OL]. BMC Bioinformatics, 2017, 18(1)：183[2023-03-19].https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1579-y.

WANG JB, PU SB, SUN Y, et al. Metabolomic profiling of autoimmune hepatitis: the diagnostic utility of nuclear magnetic resonance spectroscopy[J]. J Proteome Res, 2014, 13(8)：3792-3801.

NING ZC, LU C, ZHANG YX, et al. Application of plant metabonomics in quality assessment for large-scale production of traditional Chinese medicine[J]. Planta Med, 2013, 79(11)：897-908.

ZARIC BL, RADOVANOVIC JN, GLUVIC Z, et al. Atherosclerosis linked to aberrant amino acid metabolism and immunosuppressive amino acid catabolizing enzymes[J/OL]. Front Immunol, 2020, 11: 551758[2023-03-19]. https://www.frontiersin.org/article/10.3389/fimmu.2020.551758/full.

HOLEAČGEK M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements[J/OL]. Nutr Metab, 2018, 15: 33[2023-03-19].https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-018-0271-1.

BHATTACHARYA S, GRANGER CB, CRAIG D, et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization[J]. Atherosclerosis, 2014, 232(1)：191-196.

BURRAGE LC, NAGAMANI SC, CAMPEAU PM, et al. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders[J/OL]. Hum Mol Genet, 2014, 23(R1)：R1-R8 [2023-03-19]. https://academic.oup.com/hmg/article/23/R1/R1/2900649?login=true.

HARRIS RA, JOSHI M, JEOUNG NH, et al. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism[J]. J Nutr, 2005, 135(6 Suppl)：1527-1530.

MINIHANE AM, VINOY S, RUSSELL WR, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation[J]. Br J Nutr, 2015, 114(7)：999-1012.

ZHU Q, WU YL, MAI JX, et al. Comprehensive metabolic profiling of inflammation indicated key roles of glycerophospholipid and arginine metabolism in coronary artery disease[J/OL]. Front Immunol, 2022, 13: 829425 [2023-03-19].https://www.frontiersin.org/articles/10.3389/fimmu.2022.829425/full.

ROLIM AE, HENRIQUE-ARAÚJO R, FERRAZ EG, et al. Lipidomics in the study of lipid metabolism: current perspectives in the omic sciences[J]. Gene, 2015, 554(2)：131-139.

HA CY, KIM JY, PAIK JK, et al. The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes[J]. Clin Endocrinol, 2012, 76(5)：674-682.

LAAKSONEN R, EKROOS K, SYSI-AHO M, et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol[J]. Eur Heart J, 2016, 37(25)：1967-1976.

赖金胜，陈琛. 花生四烯酸的细胞色素P450酶代谢途径产物EETs和20-HETE在血管功能调控中的作用[J]. 生理学报，2021, 73(4)：631-645.

杨冠林，翟琼，董馨，等. 基于脂质组学技术发现冠心病的脂质标志物和治疗靶点[J]. 药学学报，2022, 57(7)：2003-2011.

HILVO M, VASILE VC, DONATO LJ, et al. Ceramides and ceramide scores: clinical applications for cardiometabolic risk stratification[J/OL]. Front Endocrinol, 2020, 11: 570628[2023-03-19]. https://www.frontiersin.org/articles/10.3389/fendo.2020.570628/full.

ECHOUFFO-TCHEUGUI JB, JAIN M, CHENG S. Breaking through the surface: more to learn about lipids and cardiovascular disease[J]. J Clin Invest, 2020, 130(3)：1084-1086.

常世敏，张智强. 浅谈维生素A代谢与生理功能[J]. 中国食物与营养，2005, 11(2)：55-57.

SUN Q, KIERNAN UA, SHI L, et al. Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study[J]. Circulation, 2013, 127(19)：1938-1947.

FARJO KM, FARJO RA, HALSEY S, et al. Retinol-binding protein 4 induces inflammation in human endothelial cells by an NADPH oxidase- and nuclear factor kappa B-dependent and retinol-independent mechanism[J]. Mol Cell Biol, 2012, 32(24)：5103-5115.

刘羽茜. 冠心病稳定型心绞痛脾虚痰浊证患者血清代谢组学研究[D]. 沈阳：辽宁中医药大学，2019.

NDREPEPA G. Uric acid and cardiovascular disease[J]. Clin Chim Acta, 2018, 484: 150-163.

PATETSIOS P, SONG M, SHUTZE WP, et al. Identification of uric acid and xanthine oxidase in atherosclerotic plaque[J]. Am J Cardiol, 2001, 88(2)：188-191.

HEINRICH M, BORK PM, SCHMITZ ML, et al. Pheophorbide A from Solanum diflorum interferes with NF-kappa B activation[J]. Planta Med, 2001, 67(2)：156-157.

SUBRAMONIAM A, ASHA VV, NAIR SA, et al. Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α gene by the same[J]. Inflammation, 2012, 35(3)：959-966.

KOIVISTO AP, BELVISI MG, GAUDET R, et al. Advances in TRP channel drug discovery: from target validation to clinical studies[J]. Nat Rev Drug Discov, 2022, 21(1)：41-59.

WATANABE H, MURAKAMI M, OHBA T, et al. TRP channel and cardiovascular disease[J]. Pharmacol Ther, 2008, 118(3)：337-351.

INOUE R, KURAHARA LH, HIRAISHI K. TRP channels in cardiac and intestinal fibrosis[J]. Semin Cell Dev Biol, 2019, 94: 40-49.

AGUS A, PLANCHAIS J, SOKOL H. Gut microbiota regulation of tryptophan metabolism in health and disease[J]. Cell Host Microbe, 2018, 23(6)：716-724.

LIU G, CHEN S, ZHONG J, et al. Crosstalk between tryptophan metabolism and cardiovascular disease, mechanisms, and therapeutic implications[J/OL]. Oxid Med Cell Longev, 2017, 2017: 1602074[2023-03-19]. https://www.hindawi.com/journals/omcl/2017/1602074/.

KOOPMAN N, KATSAVELIS D, HOVE AST, et al. The multifaceted role of serotonin in intestinal homeostasis[J/OL]. Int J Mol Sci, 2021, 22(17)：9487[2023-03-19]. https://www.mdpi.com/1422-0067/22/17/9487.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

溃疡性结肠炎活动期大肠湿热证患者血清代谢组学特征分析

基于冠状动脉CT血管成像影像组学的稳定型心绞痛痰瘀互结证与气虚血瘀证鉴别研究

基于脾脏代谢组学研究肿节风总黄酮治疗免疫性血小板减少症的作用机制

大肠癌脾虚湿热证和湿热蕴结证临床表型组的代谢组学机制

双补丸干预雷公藤多苷致生殖损伤的作用及代谢组学分析