Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis

Yu-chen QI; Lin-zhen ZOU; Xue-yan HAN; Hai-qiang JIANG; Yun-lun LI

doi:10.13422/j.cnki.syfjx.20220311

您当前的位置：

首页 >

文章列表页 >

Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis

更新时间：2022-02-07

- Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 5, Pages: 178-186(2022)
- 作者机构：
  
  1.山东中医药大学，济南 250355
  2.山东中医药大学附属医院，济南 250014
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220311
  CLC： R285;R289;R22;R2-031;R33
- Received：20 August 2021，
  
  Published Online：30 December 2021，
  
  Published：05 March 2022
- 稿件说明：
移动端阅览
齐于辰,邹琳蓁,韩学艳等.基于代谢组学和网络分析探讨胆汁酸在高血压进展中的潜在作用机制[J].中国实验方剂学杂志,2022,28(05):178-186.

QI Yu-chen,ZOU Lin-zhen,HAN Xue-yan,et al.Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):178-186.
齐于辰,邹琳蓁,韩学艳等.基于代谢组学和网络分析探讨胆汁酸在高血压进展中的潜在作用机制[J].中国实验方剂学杂志,2022,28(05):178-186. DOI： 10.13422/j.cnki.syfjx.20220311.

QI Yu-chen,ZOU Lin-zhen,HAN Xue-yan,et al.Underlying Mechanisms of Bile Acids in Progression of Hypertension Based on Metabolomics and Network Analysis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):178-186. DOI： 10.13422/j.cnki.syfjx.20220311.

摘要

目的

探讨胆汁酸及其代谢物在高血压前期的潜在作用机制，探索高血压前期的关键代谢途径和重要内源性靶点。

方法

采用非靶向代谢组学和网络分析相结合的方法探讨高血压前期的代谢机制，用超高效液相色谱-四极杆飞行时间串联质谱联用技术对高血压前期患者进行血清代谢组学分析，通过网络分析预测并生成相关的生物功能和信号目标，最终通过体外实验验证该重要途径的预测靶点，用酶联免疫吸附测定法（ELISA）和蛋白免疫印迹法（Western blot）实验分析并验证相关靶点信息。

结果

采用非靶向代谢组学方法，发现在正常组、高血压前期组和高血压组中有64个潜在的生物标志物及13条代谢途径；网络分析和生物学验证结果表明，高血压前期的发生与胆汁酸和芳香族氨基酸代谢异常引起的血管炎症有关；胆汁酸代谢通过调节血管炎症反应在高血压前期的发生发展中起重要作用；氨基酸

-酰基转移酶、髓过氧化物酶及胆酸汁受体TGR5在代谢网络的变化中具有重要意义。

结论

在高血压前期，胆汁酸可能参与调节血管炎症，从而导致高血压前期血管损伤。

Abstract

Objective

To explore the underlying mechanism of bile acids and metabolites as well as the key metabolic pathways and important endogenous targets in prehypertension.

Method

The metabolic mechanism of prehypertension was explored with non-targeted metabolomics combined with network analysis. The serum metabolomics of patients with prehypertension was analyzed by ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The relevant biological functions and signal targets were predicted and generated by network analysis. Finally，the predicted targets of this important pathway were verified by

in vitro

experiments，and the relevant information was verified by enzyme-linked immunosorbent assay （ELISA） and Western blot.

Result

As revealed by non-targeted metabolomics，there were 64 potential biomarkers and 13 metabolic pathways in the normal group，the prehypertension group， and the hypertension group. The results of network analysis and biological verification showed that the occurrence of prehypertension was related to vascular inflammation caused by the abnormal metabolism of bile acids and aromatic amino acids. Bile acid metabolism plays an important role in the occurrence and development of prehypertension by regulating the vascular inflammatory response. Amino acid

-acyltransferase，myeloperoxidase， and bile acid downstream receptor TGR5 are critical in the changes of the metabolic network.

Conclusion

In prehypertension，bile acids are presumedly involved in regulating vascular inflammation， resulting in damage to blood vessels in prehypertension.

关键词

Keywords

references

XU T ， LIU J ， ZHU G ， et al . Prevalence of prehypertension and associated risk factors among Chinese adults from a large-scale multi-ethnic population survey ［J］. BMC Public Health ， 2016 ， 16 （ 1 ）： 775 .

CHOBANIAN A V ， BAKRIS G L ， BLACK H R ， et al . The seventh report of the Joint national committee on prevention， detection， evaluation， and treatment of high blood pressure： the JNC 7 report ［J］. JAMA ， 2003 ， 289 （ 19 ）： 2560 - 2572 .

EGAN B M ， STEVENS-FABRY S . Prehypertension-prevalence，health risks，and management strategies ［J］. Nat Rev Cardiol ， 2015 ， 12 ： 289 - 300 .

HUANG Y ， WANG S ， CAI X Y ， et al . Prehypertension and incidence of cardiovascular disease：a Meta-analysis ［J］. BMC Med ， 2013 ， 11 ： 177 .

GE Q ， YUAN W ， ZHOU J Y ， et al . Correlation between arterial stiffness and left ventricular diastolic function in prehypertension ［J］. J Jiangsu University （Medicine version）， 2015 ， 25 ： 326 - 330 .

ANDRADE J ， KHAIRY P ， DOBREV D ， et al . The clinical profile and pathophysiology of atrial fibrillation： relationships among clinical features， epidemiology， and mechanisms ［J］. Circ Res ， 2014 ， 114 （ 9 ）： 1453 - 1468 .

WANG H J ， WANG X M ， QI D M ， et al . Establishment of the circadian metabolic phenotype strategy in spontaneously hypertensive rats：a dynamic metabolomics study ［J］. J Transl Med ， 2020 ， 18 ： 38 .

YANG W ， DENG Y ， ZHOU H ， et al . Metabolic characteristics of Rhizoma Coptidis intervention in spontaneously hypertensive rats： insights gained from metabolomics analysis of serum ［J］. Mol Med Rep ， 2017 ， 16 （ 4 ）： 4301 - 4308 .

XU J W ， LI Y L ， ZhANG S J ， et al . Quantitative serum proteomic analysis of essential hypertension using iTRAQ technique ［J］. Biomed Res Int ， 2017 ， 2017 ： 6761549 .

KUNDU S ， BANSAL S ， MUTHUKUMARASAMY K M ， et al . Deciphering the role of hydrophobic and hydrophilic bile acids in angiogenesis using in vitro and in vivo model systems ［J］. Med Chem Comm ， 2017 ， 8 （ 12 ）： 2248 - 2257

WU F ， ZHENG H ， YANG Z T ， et al . Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using 1 HNMR analysis ［J］. J Pharmaceut Biomed Anal ， 2017 ， 140 ： 199 - 209 .

LOU G ， MA X ， FU X ， et al . GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells ［J］. PLoS One ， 2014 ， 9 （ 4 ）： e93567 .

KEITEL V ， REINEHR R ， GATSIOS P ， et al . The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells ［J］. Hepatology ， 2007 ， 45 （ 3 ）： 695 - 704 .

WANG X X ， WANG D ， LUO Y ， et al . FXR/TGR5 dual agonist prevents progression of nephropathy in diabetes and obesity ［J］. J Am Soc Nephrol ， 2018 ， 29 （ 1 ）： 118 - 137 .

JELLINGER K A . The role of iron in neurodegeneration： prospects for pharmacotherapy of Parkinson's disease ［J］. Drugs Aging ， 1999 ， 14 （ 2 ）： 115 - 140 .

BANEGAS I ， PRIETO I ， SEGARRA A B ， et al . Blood pressure increased dramatically in hypertensive rats after left hemisphere lesions with 6-hydroxydopamine ［J］. Neurosci Lett ， 2011 ， 500 （ 2 ）： 148 - 150 .

陈纪烨，周国锋，王永成，等 . 桂枝汤桂枝-白芍不同比例配伍通过调节TGF- β 1 /Smads信号通路及慢性炎症改善盐敏感高血压大鼠心肌纤维化［J］. 中国实验方剂学杂志， 2020 ， 26 （ 1 ）： 50 - 58 .

ALBARWANI S ， AL-SIYABI S ， TANIRA M O . Prehypertension：underlying pathology and therapeutic Options ［J］. World J Cardiol ， 2014 ， 6 ： 728 - 743 .

MIYAZAKI-ANZAI S ， MASUDA M ， KOHNO S ， et al . Simultaneous inhibition of FXR and TGR5 exacerbates atherosclerotic formation ［J］. J Lipid Res ， 2018 ， 59 （ 9 ）： 1709 - 1713 .

KIDA T ， OMORI K ， HORI M . Stimulation of G protein-coupled bile acid receptor enhances vascular endothelial barrier function via activation of protein kinase A and Rac1 ［J］. J Pharmacol Experiment Therapeut ， 2014 ， 348 ： 125 - 130 .

KHALILOVA I S ， DICKERHOF N ， MOCATTA T J ， et al . A myeloperoxidase precursor， pro-myeloperoxidase， is present in human plasma and elevated in cardiovascular disease patients ［J］. PLoS One ， 2018 ， 13 （ 3 ）： e0192952 .

GETEHELL J P ， WROBLEWSKI K E ， DEMARIA A ， et al . Testing for HCV infection：an update of guidance for elinicians and laboratorians ［J］. Morb Mortal Wkly Rep ， 2013 ， 62 ： 362 - 365 .

ZHANG R ， BRENNAN M L ， SHEN Z ， et al . Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation ［J］. J Biol Chem ， 2002 ， 277 （ 48 ）： 46116 - 46122 .

HADžIć N ， BULL L N ， CLAYTON P T ， et al . Diagnosis in bile acid-CoA： amino acid N-acyltransferase deficiency ［J］. World J Gastroenterol ， 2012 ， 18 （ 25 ）： 3322 - 3326 .

QIN P ， TANG X ， ELLOSO M M ， et al . Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species， NF-kappaB， and p38 ［J］. Am J Physiol Heart Circ Physiol ， 2006 ， 291 （ 2 ）： H741 - 747 .

STEPANOV V ， STANKOV K ， MIKOV M . The bile acid membrane receptor TGR5： a novel pharmacological target in metabolic， inflammatory and neoplastic disorders ［J］. J Recept Signal Transduct Res ， 2013 ， 33 （ 4 ）： 213 - 223 .

HAGEMAN J ， HERREMA H ， GROEN A K ， et al . A role of the bile salt receptor FXR in atherosclerosis ［J］. Arterioscler Thromb Vasc Biol ， 2010 ， 30 （ 8 ）： 1519 - 1528 .

WATANABE M ， HOUTEN S M ， MATAKI C ， et al . Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation ［J］. Nature ， 2006 ， 439 （ 7075 ）： 484 - 489 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Metabolomics Analysis of Plasma at Different Stages Based on UPLC-Q-TOF/MS： Modeling of Spleen Deficiency with Dampness Retention-ulcerative Colitis Rats and Administration of Shenling Baizhusan

Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics

Establishment and Evaluation of Mouse Model of Cerebral Infarction with Qi and Yin Deficiency Syndrome Based on Metabolomics

Differences and Mechanisms of Combined Use of "Raw and Fried Ziziphi Spinosae Semen" in Anmeidan and Its Disassembled Prescriptions in Improving Anxiety and Cognitive Impairment in Insomnia Rat Model Based on Serum Metabolomics

Effect of Anmeidan on Cognitive Function and Metabolic Profiling in Insomnia Model Rats Based on Untargeted Metabolomics

Related Author

Xia XU

Weiwei WANG

Wentong ZHANG

Yanling XIONG

Bingtao LI

Qiyun ZHANG

Guoliang XU

Li JIANG

Related Institution

Research Center for Differentiation and Development of Traditional Chinese Medicine（TCM） Basic Theory，Jiangxi Province Key Laboratory of TCM Etiopathogenisis，Jiangxi Key Laboratory of Pharmacology of TCM，Jiangxi University of Chinese Medicine

Affiliated Hospital of Jinggangshan University

Institute of Clinical Pharmacology，Xiangya Hospital，Central South University

School of Clinical Medicine，Beijing University of Chinese Medicine

Beijing Key Laboratory of Chinese Materia Pharmacology，National Clinical Research Center of Traditional Chinese Medicine for Cardiovascular Diseases，Institute of Basic Medical Sciences， Xiyuan Hospital，China Academy of Chinese Medical Sciences

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰