高血压代谢组学差异代谢物与代谢通路的研究进展

李东烨 ,  朱润荷 ,  朱晓倩 ,  宗芮羽 ,  崔竞茹 ,  高红梅

中华高血压杂志(中英文) ›› 2026, Vol. 34 ›› Issue (6) : 518 -526.

PDF (1251KB)
中华高血压杂志(中英文) ›› 2026, Vol. 34 ›› Issue (6) : 518 -526. DOI: 10.16439/j.issn.1673-7245.2025-0278
综述

高血压代谢组学差异代谢物与代谢通路的研究进展

作者信息 +

Research progress on differential metabolites and metabolic pathways in hypertension based on metabolomics

Author information +
文章历史 +
PDF (1280K)

摘要

本文旨在基于血清代谢组学技术,分析原发性高血压患者差异代谢物及相关代谢通路,为高血压的早期诊断和精准治疗提供新视角。通过综述现有研究,系统总结原发性高血压患者氨基酸代谢、脂肪酸代谢、氧化应激、类固醇激素代谢及其他代谢异常等多条代谢通路的异常变化及其与血压调控的关联。原发性高血压患者存在显著的氨基酸代谢紊乱,尤其是支链氨基酸、丙氨酸和精氨酸水平与血压密切相关;短链脂肪酸的代谢紊乱可通过影响血管舒缩功能影响血压水平;氧化应激可促进血管内皮损伤与收缩;类固醇激素如醛固酮和皮质醇可通过调节肾素-血管紧张素-醛固酮系统及钠水潴留加剧高血压:多种代谢通路相互作用共同促进疾病进展。代谢紊乱在原发性高血压的发生发展中起关键作用,代谢组学分析有助于揭示其病理机制,并为早期干预和靶向治疗提供理论依据。

Abstract

This review aims to analyze differential metabolites and metabolic pathways in essential hypertension based on serum metabolomics, providing new insights for early diagnosis and precise treatment. Through a comprehensive review of existing studies, this paper systematically summarized abnormalities in multiple metabolic pathways—including amino acid metabolism, fatty acid metabolism, oxidative stress, steroid hormone metabolism, and other metabolic disturbances—and their associations with blood pressure regulation. Patients with essential hypertension exhibit significant disturbances in amino acid metabolism, with levels of branched-chain amino acids, alanine, and arginine being closely associated with blood pressure. Dysregulation of short-chain fatty acid metabolism may influence blood pressure by affecting vasomotor function. Oxidative stress promotes endothelial injury and vasoconstriction. Steroid hormones such as aldosterone and cortisol may exacerbate hypertension by activating the renin-angiotensin-aldosterone system and promoting sodium and water retention. The interplay among multiple metabolic pathways collectively drives disease progression. Metabolic disorders play a critical role in the pathogenesis of essential hypertension. Metabolomic analysis helps elucidate underlying mechanisms and offers a theoretical basis for early intervention and targeted therapy.

关键词

原发性高血压 / 代谢组学 / 差异代谢物 / 代谢通路 / 代谢紊乱

Key words

essential hypertension / metabolomics / differential metabolites / metabolic pathways / metabolic disorders

引用本文

引用格式 ▾
李东烨,朱润荷,朱晓倩,宗芮羽,崔竞茹,高红梅. 高血压代谢组学差异代谢物与代谢通路的研究进展[J]. 中华高血压杂志(中英文), 2026, 34(6): 518-526 DOI:10.16439/j.issn.1673-7245.2025-0278

登录浏览全文

4963

注册一个新账户 忘记密码

参考文献

[1]

依丽达尔·依布拉音, 梁晓慧 . 原发性高血压患者甘油三酯—葡萄糖指数与中心动脉压相关指标的关系[J]. 中国医刊202560(9): 1050-1053.

[2]

Klassen A, Faccio AT, Canuto GA, et al. Metabolomics: definitions and significance in systems biology[J]. Adv Exp Med Biol2017965: 3-17.

[3]

欧阳辉, 付海艳, 杜映荣 . 组学技术在原发性高血压中的应用进展[J]. 实用心脑肺血管病杂志202230(9): 118-123.

[4]

王霄霄, 王海霞, 左德筠 . 原发性高血压的代谢组学研究现状[J]. 吉林医学201940(5): 1109-1112.

[5]

Poggiogalle E, Fontana M, Giusti AM, et al. Amino acids and hypertension in adults[J]. Nutrients201911(7): 1459.

[6]

Zhong L, Zhang JP, Nuermaimaiti AG, et al. Study on plasmatic metabolomics of Uygur patients with essential hypertension based on nuclear magnetic resonance technique[J]. Eur Rev Med Pharmacol Sci201418(23): 3673-3680.

[7]

林震, 刘志远, 张富洋, . 支链氨基酸与代谢性心血管疾病关系研究进展[J]. 空军军医大学学报202546(2): 266-272.

[8]

Fujii T, Yura S, Tatsumi K, et al. Branched—chain amino acid supplemented diet during maternal food restriction prevents developmental hypertension in adult rat offspring[J]. J Dev Orig Health Dis20112(3): 176-183.

[9]

Du C, Xu H, Zhao W, et al. Inhibiting SLC38A2 lowers blood pressure in rodent models of hypertension[J]. Sci Transl Med202517(814): eadt5947.

[10]

国家心血管病中心国家基本公共卫生服务项目基层高血压管理办公室, 国家基层高血压管理专家委员会 . 国家基层高血压防治管理指南 2025 版[J]. 中国循环杂志202540(9): 836-850.

[11]

Han C, Jiang YH, Li W, et al. Study on the antihypertensive mechanism of Astragalus membranaceus and Salvia miltiorrhiza based on intestinal flora—host metabolism[J]. Evid Based Complement Alternat Med20192019: 5418796.

[12]

Wu S, Zhao W, Yu Z . Novel targets and potential mechanisms of mizuhopecten yessoensis—derived tripeptide NCW as antihypertensive peptides[J]. Mol Nutr Food Res202468(14): e2300552.

[13]

陈珅, 李卿, 林文静, . 血清 FABP4、PECAM—1 在中青年原发性高血压患者中的表达及临床意义[J]. 中国分子心脏病学杂志202323(5): 5669-5674.

[14]

吕晓霞, 李君, 李芳 . 血清 CypA、OPG、FABP4 与妊娠期糖尿病合并高血压患者炎症因子的相关性分析[J]. 中国妇产科临床杂志202122(3): 293-294.

[15]

De La Visitación N, Robles—Vera I, Moleón J, et al. Gut microbiota has a crucial role in the development of hypertension and vascular dysfunction in toll—like receptor 7—driven lupus autoimmunity[J]. Antioxidants202110(9): 1426.

[16]

Nguyen H, Chiasson VL, Chatterjee P, et al. Interleukin—17 causes Rho—kinase—mediated endothelial dysfunction and hypertension[J]. Cardiovasc Res201397(4): 696-704.

[17]

Cifuentes MP, Chapman JA, Stewart CJ . Gut microbiome derived short chain fatty acids: promising strategies in necrotising enterocolitis[J]. Curr Res Microb Sci20246: 100219.

[18]

Robles—Vera I, Toral M, Duarte J . Microbiota and hypertension: role of the sympathetic nervous system and the immune system[J]. Am J Hypertens202033(10): 890-901.

[19]

Liu H, Zhuang J, Tang P, et al. The role of the gut microbiota in coronary heart disease[J]. Curr Atheroscler Rep202022(12): 77.

[20]

Mehanna M, McDonough CW, Smith SM, et al. Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers[J]. Clin Transl Sci202417(5): e13816.

[21]

R Muralitharan R, Zheng T, Dinakis E, et al. Gut microbiota metabolites sensed by host GPR41/43 protect against hypertension[J]. Circ Res2025136(4): e20-e33.

[22]

Li Z, Hao E, Cao R, et al. Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups[J]. Chin Herb Med202214(4): 479-493.

[23]

郅季炘, 王甜甜, 任爽, . 高强度间歇运动通过调控氧化应激改善原发性高血压患者内皮祖细胞功能[J]. 环境与职业医学202542(2): 179-187.

[24]

Watson T, Goon PK, Lip GY . Endothelial progenitor cells, endothelial dysfunction, inflammation, and oxidative stress in hypertension[J]. Antioxid Redox Signal200810(6): 1079-1088.

[25]

Tain YL, Hsu CN . Oxidative stress—induced hypertension of developmental origins: preventive aspects of antioxidant therapy[J]. Antioxidants202211(3): 511.

[26]

Franco C, Sciatti E, Favero G, et al. Essential hypertension and oxidative stress: novel future perspectives[J]. Int J Mol Sci202223(22): 14489.

[27]

Baradaran A, Nasri H, Rafieian—Kopaei M . Oxidative stress and hypertension: possibility of hypertension therapy with antioxidants[J]. J Res Med Sci201419(4): 358-367.

[28]

Laursen JB, Somers M, Kurz S, et al. Endothelial regulation of vasomotion in ApoE—deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin[J]. Circulation2001103(9): 1282-1288.

[29]

Ghezzi P, Jaquet V, Marcucci F, et al. The oxidative stress theory of disease: levels of evidence and epistemological aspects[J]. Br J Pharmacol2017174(12): 1784-1796.

[30]

Feairheller DL, Brown MD, Park JY, et al. Exercise training, NADPH oxidase p22phox gene polymorphisms, and hypertension[J]. Med Sci Sports Exerc200941(7): 1421-1428.

[31]

Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape—seed polyphenols increases blood pressure: a randomized, double—blind, placebo—controlled trial[J]. J Hypertens200523(2): 427-434.

[32]

Craighead DH, Freeberg KA, Heinbockel TC, et al. Time—efficient, high—resistance inspiratory muscle strength training increases exercise tolerance in midlife and older adults[J]. Med Sci Sports Exerc202456(2): 266-276.

[33]

Toghi CJ, Martins LZ, Pacheco LL, et al. Pravastatin prevents increases in activity of metalloproteinase—2 and oxidative stress, and enhances endothelium—derived nitric oxide—dependent vasodilation in gestational hypertension[J]. Antioxidants (Basel)202312(4): 939.

[34]

Touyz RM, Rios FJ, Alves—Lopes R, et al. Oxidative stress: a unifying paradigm in hypertension[J]. Can J Cardiol202036(5): 659-670.

[35]

Dikalov SI, Nazarewicz RR . Angiotensin Ⅱ—induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease[J]. Antioxid Redox Signal201319(10): 1085-1094.

[36]

Swenja K, Sebastian S, Sabine K, et al. Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species—studies in white blood cells and in animal models[J]. Antioxid Redox Signal201420(2): 247-266.

[37]

Müllebner A, Dorighello GG, Kozlov AV, et al. Interaction between mitochondrial reactive oxygen species, heme oxygenase, and nitric oxide synthase stimulates phagocytosis in macrophages[J]. Front Med (Lausanne)20174: 252.

[38]

徐琬, 魏婷婷, 李若兰, . 常见减重饮食模式对血压影响的研究进展[J]. 中华高血压杂志 (中英文)202533(9): 822-827.

[39]

Liu X, Xu X, Zhang T, et al. Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases[J]. Phytother Res202337(11): 4976-4998.

[40]

屈春乐, 杨宁, 李玉明 . 妊娠期高血压疾病的早期预防[J]. 中华高血压杂志 (中英文)202533(4): 328-334.

[41]

高晓梅, 侯敬侠 . 高血压患者肾素、醛固酮、血管紧张素Ⅱ、皮质醇水平变化及意义[J]. 中国卫生工程学202423(6): 790-792.

[42]

屈丰雪, 曾荣, 闫家富, . 原发性高血压患者升主动脉内径与肾素血管紧张素醛固酮系统的相关性研究[J]. 心肺血管病杂志202241(7): 762-767.

[43]

Ferreira NS, Tostes RC, Paradis P, et al. Aldosterone, inflammation, immune system, and hypertension[J]. Am J Hypertens202134(1): 15-27.

[44]

Gomes RA, Ld T, Lopes IC, et al. Angiotensin—converting enzyme in pericardial fluid: comparative study with serum activity[J]. Arq Bras Cardiol200891(3): 156-161,172— 178.

[45]

Orlov SN, Mongin AA . Salt—sensing mechanisms in blood pressure regulation and hypertension[J]. Am J Physiol Heart Circ Physiol2007293(4): H2039-H2053.

[46]

刘海伦, 周婧彧, 郑静静, . 高血压非药物治疗研究进展[J]. 中华高血压杂志202331(11): 1117-1123.

[47]

Ponticelli C, Podestà MA, Moroni G . Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease[J]. Kidney Int202098(5): 1149-1159.

[48]

Korsmo HW, Ekperikpe US, Daehn IS . Emerging roles of xanthine oxidoreductase in chronic kidney disease[J]. Antioxidants (Basel)202413(6): 712.

[49]

申艳梅, 李慧芳, 李雅, . 不同糖耐量受损人群血清脂肪因子表达与胰岛素抵抗的关系及其预测糖尿病前期病情进展风险的价值[J]. 实用临床医药杂志202428(23): 116-120, 131.

[50]

罗静 . 2 型糖尿病胰岛素抵抗与心血管疾病的研究进展[J]. 公共卫生与预防医学202334(5): 125-128.

[51]

王禹捷, 吴璨, 武楷文, . 基于孟德尔随机化探索肠道微生物和血液代谢物与高血压及其并发症之间的因果关系[J]. 心血管病学进展202445(11): 1039-1045.

[52]

Zhenyukh O, González—Amor M, Rodrigues—Diez RR, et al. Branched—chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation[J]. J Cell Mol Med201822(10): 4948-4962.

[53]

宋伟, 李光辉 . 与肥胖相关的短链脂肪酸水平失衡对妊娠期高血压疾病影响的研究进展[J]. 医学综述202127(24): 4805-4810.

[54]

Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory receptor responding to gut microbiota—derived signals plays a role in renin secretion and blood pressure regulation[J]. Proc Natl Acad Sci U S A2013110(11): 4410-4415.

[55]

Benjamin. Correction to: Heart disease and stroke statistics—2017 update: a report from the American Heart Association[J]. Circulation2017135(10): e646.

[56]

刘宇, 毕颖斐, 胡珍, . 冠心病不同证候的生物标志物特征研究进展[J]. 中国中医药信息杂志202128(7): 133-136.

[57]

Zhang ZY, Marrachelli VG, Yang WY, et al. Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study[J]. Eur J Prev Cardiol201926(1): 22-32.

[58]

Wang W, Zhang F, Xia Y, et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction[J]. Am J Physiol Heart Circ Physiol2016311(5): H1160-H1169.

[59]

Li Y, Xiong Z, Yan W, et al. Branched chain amino acids exacerbate myocardial ischemia/reperfusion vulnerability via enhancing GCN2/ATF6/PPAR—α pathway—dependent fatty acid oxidation[J]. Theranostics202010(12): 5623-5640.

[60]

Amara M, Stoler O, Birati YE . The role of inflammation in the pathophysiology of heart failure[J]. Cells2025, 14(14): 1117.

[61]

Chaikijurajai T, Tang W . Reappraisal of inflammatory biomarkers in heart failure[J]. Curr Heart Fail Rep202017(1): 9-19.

[62]

Kacerova T, Pires E, Walsby—Tickle J, et al. Integrating NMR and multi—LC—MS—based untargeted metabolomics for comprehensive analysis of blood serum samples[J]. Anal Chim Acta20251356: 343979.

[63]

Zeki ÖC, Eylem CC, Reçber T, et al. Integration of GC—MS and LC—MS for untargeted metabolomics profiling[J]. J Pharm Biomed Anal2020190: 113509.

[64]

Lapris M, Errico M, Rocchetti G, et al. The potential of multi—screening methods and omics technologies to detect both regulated and emerging mycotoxins in different matrices[J]. Foods202413(11): 1746.

[65]

Raza A. Metabolomics: a systems biology approach for enhancing heat stress tolerance in plants[J]. Plant Cell Rep202241(3): 741-763.

[66]

Halket JM, Waterman D, Przyborowska AM, et al. Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS[J]. J Exp Bot200556(410): 219-243.

[67]

Wei Z, Rawi R . CE—MS for metabolomics: developments and applications in the period 2018—2020.[J]. Electrophoresis202042(4): 381-401.

[68]

Ramautar R, de Jong GJ . Recent developments in liquid—phase separation techniques for metabolomics[J]. Bioanalysis20146(7): 1011-1026.

[69]

Padmanabhan S, Tran T, Dominiczak AF . Artificial intelligence in hypertension: seeing through a glass darkly[J]. Circ Res2021128(7): 1100-1118.

[70]

Cho JS, Park JH . Application of artificial intelligence in hypertension[J]. Clin Hypertens202430(1): 11.

[71]

Naik A, Nalepa J, Wijata AM, et al. Artificial intelligence and digital twins for the personalised prediction of hypertension risk[J]. Comput Biol Med, 2025, 196(Pt A): 110718.

[72]

Alabed S, Uthoff J, Zhou S, et al. Machine learning cardiac—MRI features predict mortality in newly diagnosed pulmonary arterial hypertension[J]. Eur Heart J Digit Health20223(2): 265-275.

[73]

Khan SM, He F, Wang D, et al. MU—PseUDeep: a deep learning method for prediction of pseudouridine sites[J]. Comput Struct Biotechnol J202018: 1877-1883.

[74]

Parastar H, Tauler R . Big (Bio)chemical data mining using chemometric methods: a need for chemists[J]. Angew Chem Int Ed Engl202261(44): e201801134.

[75]

Flores—Guerrero JL, Groothof D, Connelly MA, et al. Concentration of branched—chain amino acids is a strong risk marker for incident hypertension[J]. Hypertension201974(6): 1428-1435.

[76]

Yu L, Zhu Q, Song P, et al. Dietary branched—chain amino acids intake and new—onset hypertension: a nationwide prospective cohort study in China[J]. Amino Acids202456(1): 19.

[77]

Tran SK, Ngo TH, Nguyen PH, et al. Hyperhomocysteinemia in patients with newly diagnosed primary hypertension in Can Tho City, Vietnam[J]. Healthcare202311(2): 234.

[78]

Hidru TH, Yang X, Xia Y, et al. The relationship between plasma markers and essential hypertension in middle—aged and elderly Chinese population: a community based cross—sectional study[J]. Sci Rep20199(1): 6813.

[79]

Xiong Y, Jiang L, Li T . Aberrant branched—chain amino acid catabolism in cardiovascular diseases[J]. Front Cardiovasc Med20229: 965899.

[80]

张啸, 王冬凌, 刘剑刚 . 基于代谢组学技术分析益气活血中药复方治疗慢性心力衰竭的作用机制[J]. 中西医结合心脑血管病杂志202422(23): 4235-4243.

[81]

齐涵, 杨晓俊, 温馥源, . 多组学大数据分析方法在高血压研究中的应用进展[J]. 中华高血压杂志 (中英文)202432(2): 119-126.

[82]

Sekaran K, Zayed H . Identification of novel hypertension biomarkers using explainable AI and metabolomics[J]. Metabolomics202420(6): 124.

基金资助

国家自然科学基金项目(82104844)

泰山学者工程专项经费资助(tsqn202507381)

山东省中医药科技项目面上项目(M20241912)

AI Summary AI Mindmap
PDF (1251KB)

4

访问

0

被引

详细

导航
相关文章

AI思维导图

/