基于不同生物样本代谢组学的OSAHS生物标志物研究进展

doi:10.16150/j.1671-2870.2022.04.021

摘要/Abstract

摘要：

阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea-hypopnea syndrome, OSAHS）是一种以呼吸暂停、低通气、微觉醒等为主要临床表现的睡眠障碍性疾病,其主要病理生理机制为上气道狭窄。目前,OSAHS的发病率呈逐年上升的趋势,但其临床诊断方法仍比较单一,无法做到早期精确诊断。代谢组学作为国际上新兴的一门学科,虽然目前技术发展时间相对较短,但已在医学、药学、毒理学等多个领域获得较大突破,发挥着越来越重要的作用。本文系统回顾了代谢组学在探寻OSAHS生物标志物方面的研究和应用,发现OSAHS会导致一些特殊的代谢产物发生改变,其中包括氨基酸、脂质、酰基肉碱、肠道菌群、磷脂类、芳香烃类、饱和烃类、丙酮以及异戊二烯等,涉及氨基酸代谢、脂质代谢、氧化应激途径、磷脂代谢、内源性大麻素系统等多种代谢途径和作用机制。这些差异性代谢产物存在于患者的多种生物标本中,包括血液、尿液、粪便、唾液、扁桃体组织等,这些OSAHS代谢组学相关的生物标志物,可为早期诊断和鉴别诊断并研究发病机制提供参考。

关键词: 代谢组学, 代谢物, 阻塞性睡眠呼吸暂停低通气综合征, 生物标志物

Abstract:

The obstructive sleep apnea-hypopnea syndrome(OSAHS) is a sleep disorder caused by upper airway stenosis, and the main clinical manifestations were apnea, hypopnea, and arousal. In recent years, the incidence of OSAHS shows increasing trend, while its clinical diagnosis method is still relatively simple, and the early accurate diagnosis cannot be achieved. Metabolomics has played an important role in many disciplines such as medicine, pharmacy, and toxicology as an emerging subject, even if its research develops relatively short time. In this paper, we systematically reviewed the studies and applications of metabolomics on OSAHS biomarkers and found that OSAHS could cause changes in some special metabolites, including amino acids, lipids, acylcarnitines, intestinal flora, phospholipids, aromatic hydrocarbons, saturated hydrocarbons, acetone and isoprene. These metabolites involved in various metabolic pathways and mechanisms such as amino acid metabolism, lipid metabolism, oxidative stress pathway, phospholipid metabolism and endocannabinoids. The differential metabolites existed in a variety of biological samples in patients, including blood, urine, feces, saliva, and tonsil tissue, and some metabolites could be used in the early diagnosis and differential diagnosis of OSAHS and as the reference for further research on the biomarkers and pathogenesis of OSAHS.

Key words: Metabolomics, Metabolites, OSAHS, Biomarkers

中图分类号:

R735

周思锋, 徐海舒, 范欣生. 基于不同生物样本代谢组学的OSAHS生物标志物研究进展[J]. 诊断学理论与实践, 2022, 21(04): 535-540.

ZHOU Sifeng, XU Haishu, FAN Xinsheng. Application of metabolomics of different biological samples in study of OSAHS biomarkers[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 535-540.

参考文献 35

[1]	Zhang P, Georgiou CA, Brusic V. Elemental metabolomics[J]. Brief Bioinform, 2018, 19(3):524-536. doi: 10.1093/bib/bbw131 pmid: 28077402
[2]	唐玥, 韩宇博, 隋艳波, 等. 代谢组学技术在代谢综合征诊疗中的应用进展[J]. 医学综述, 2022, 28(3):579-583.
	Tang Y, Han YB, Sui YB, et al. Application progress of metabonomics technology in the diagnosis and treatment of metabolic syndrome[J]. Med Rev, 2022, 28(3): 579-583.
[3]	Kennedy AD, Wittmann BM, Evans AM, et al. Metabolomics in the clinic: A review of the shared and unique features of untargeted metabolomics for clinical research and clinical testing[J]. Mass Spectrom, 2018, 53(11):1143-1154. doi: 10.1002/jms.4292 URL
[4]	Chen YC, Hsu PY, Hsiao CC, et al. Epigenetics: A potential mechanism involved in the pathogenesis of various adverse consequences of obstructive sleep apnea[J]. Int J Mol Sci, 2019, 20(12):2937. doi: 10.3390/ijms20122937 URL
[5]	阻塞性睡眠呼吸暂停低通气综合征诊治指南基层版写作. 阻塞性睡眠呼吸暂停低通气综合征诊治指南(基层版)[J]. 中国呼吸与危重监护杂志, 2015, 14(4):398-405.
	Guidelines for the diagnosis and treatment of obstructive sleep apnea hypopnea syndrome(Basic Edition)[J]. Chin J Respir Crit Care, 2015, 14 (4): 398-405.
[6]	Selmi C, Montano N, Furlan R, et al. Inflammation and oxidative stress in obstructive sleep apnea syndrome[J]. Exp Biol Med (Maywood), 2007, 232(11):1409-1413. doi: 10.3181/0704-MR-103 URL
[7]	Xu H, Zheng X, Jia W, et al. Chromatography/mass spectrometry-based biomarkers in the field of obstructive sleep apnea[J]. Medicine(Baltimore), 2015, 94(40):e1541.
[8]	Pugliese G, Barrea L, Laudisio D, et al. Sleep apnea, obesity, and disturbed glucose homeostasis: epidemiologic evidence, biologic insights, and therapeutic strategies[J]. Curr Obes Rep, 2020, 9(1):30-38. doi: 10.1007/s13679-020-00369-y pmid: 31970714
[9]	Ma XR, Wang Y, Sun YC. Imbalance of osteoprotegerin/receptor activator of nuclear factor-κB ligand and oxidative stress in patients with obstructive sleep apnea-hypopnea syndrome[J]. Chin Med J (Engl), 2019, 132(1):25-29.
[10]	Kapur VK, Auckley DH, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: An american academy of sleep medicine clinical practice guideline[J]. J Clin Sleep Med, 2017, 13(3):479-504. doi: 10.5664/jcsm.6506 pmid: 28162150
[11]	罗雪梅. 代谢组学技术及其在产科的应用[J]. 国际妇产科学杂志, 2011, 38(5): 378-382.
	Luo XM. Metabonomics technology and its application in obstetrics[J]. Internl J Obstet Gynecol, 2011, 38(5):378-382.
[12]	Emwas AH. The strengths and weaknesses of NMR spectroscopy and mass spectrometry with particular focus on metabolomics research[J]. Methods Mol Biol, 2015, 1277:161-193.
[13]	贾伟. 医学代谢组学[M]. 上海: 上海科学技术出版社, 2011:98-127.
	Jia W. Medical metabolomics[M]. Shanghai: Shanghai Science and Technology Press, 2011:98-127.
[14]	Engeli S, Blüher M, Jumpertz R, et al. Circulating anandamide and blood pressure in patients with obstructive sleep apnea[J]. J Hypertens, 2012, 30(12):2345-2351. doi: 10.1097/HJH.0b013e3283591595 pmid: 23032139
[15]	Lebkuchen A, Carvalho VM, Venturini G, et al. Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk[J]. Sci Rep, 2018, 8(1):11270. doi: 10.1038/s41598-018-29727-6 pmid: 30050090
[16]	Ferrarini A, Rupérez FJ, Erazo M, et al. Fingerprinting-based metabolomic approach with LC-MS to sleep apnea and hypopnea syndrome: a pilot study[J]. Electrophoresis, 2013, 34(19):2873-2881. doi: 10.1002/elps.201300081 pmid: 23775633
[17]	Jordan W, Berger C, Cohrs S, et al. CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea syndrome[J]. J Neural Transm (Vienna), 2004, 111(6):683-689.
[18]	Niu X, Chen X, Xiao Y, et al. The differences in homocysteine level between obstructive sleep apnea patients and controls: a meta-analysis[J]. PLoS One, 2014, 9(4):e95794. doi: 10.1371/journal.pone.0095794 URL
[19]	Li K, Zhang J, Qin Y, et al. Sociation between serum homocysteine level and obstructive sleep apnea: A meta-analysis[J]. Biomed Res Int, 2017, 2017:7234528.
[20]	Chen X, Niu X, Xiao Y, et al. Effect of continuous positive airway pressure on homocysteine levels in patients with obstructive sleep apnea: a meta-analysis[J]. Sleep Breath, 2014, 18(4):687-694. doi: 10.1007/s11325-014-0940-x pmid: 24463983
[21]	Day RM, Matus IA, Suzuki YJ, et al. Plasma levels of retinoids, carotenoids and tocopherols in patients with mild obstructive sleep apnoea[J]. Respirology, 2009, 14(8):1134-1142. doi: 10.1111/j.1440-1843.2009.01623.x pmid: 19761534
[22]	Zhou L, Chen P, Peng Y, et al. Role of oxidative stress in the neurocognitive dysfunction of obstructive sleep apnea syndrome[J]. Oxid Med Cell Longev, 2016, 2016:9626831.
[23]	Dikmenoiğlu N, Ciftçi B, Ileri E, et al. Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome[J]. Sleep Med, 2006, 7(3):255-261. pmid: 16564211
[24]	Kobayashi M, Miyazawa N, Takeno M, et al. Circulating carbon monoxide level is elevated after sleep in patients with obstructive sleep apnea[J]. Chest, 2008, 134(5):904-910. doi: S0012-3692(08)60348-7 pmid: 18988776
[25]	O′Driscoll DM, Horne RS, Davey MJ, et al. Increased sympathetic activity in children with obstructive sleep apnea: cardiovascular implications[J]. Sleep Med, 2011, 12(5):483-488. doi: 10.1016/j.sleep.2010.09.015 pmid: 21521626
[26]	Paik MJ, Kim DK, Nguyen DT, et al. Correlation of daytime sleepiness with urine metabolites in patients with obstructive sleep apnea[J]. Sleep Breath, 2014, 18(3):517-523. doi: 10.1007/s11325-013-0913-5 URL
[27]	Monneret D, Pepin JL, Godin-Ribuot D, et al. Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima-media thickness in nonobese sleep apnea patients[J]. Free Radic Biol Med, 2010, 48(4):619-625. doi: 10.1016/j.freeradbiomed.2009.12.008 URL
[28]	Xu H, Zheng X, Qian Y, et al. Metabolomics profiling for obstructive sleep apnea and simple snorers[J]. Sci Rep, 2016, 6:30958. doi: 10.1038/srep30958 pmid: 27480913
[29]	Xu H, Li X, Zheng X, et al. Pediatric obstructive sleep apnea is associated with changes in the oral microbiome and urinary metabolomics profile: A pilot study[J]. J Clin Sleep Med, 2018, 14(9):1559-1567. doi: 10.5664/jcsm.7336 pmid: 30176961
[30]	Kawai M, Kirkness JP, Yamamura S, et al. Increased phosphatidylcholine concentration in saliva reduces surface tension and improves airway patency in obstructive sleep apnoea[J]. J Oral Rehabil, 2013, 40(10):758-766. doi: 10.1111/joor.12094 pmid: 24033347
[31]	Ezzedini R, Darabi M, Ghasemi B, et al. Tissue fatty acid composition in obstructive sleep apnea and recurrent tonsillitis[J]. Int J Pediatr Otorhinolaryngol, 2013, 77(6):1008-1012. doi: 10.1016/j.ijporl.2013.03.033 URL
[32]	Papandreou C. Independent associations between fatty acids and sleep quality among obese patients with obstructive sleep apnoea syndrome[J]. J Sleep Res, 2013, 22(5):569-572. doi: 10.1111/jsr.12043 pmid: 23432533
[33]	Zɖbek A, Stanimirova I, Deja S, et al. Fusion of the 1 H NMR data of serum, urine and exhaled breath condensate in order to discriminate chronic obstructive pulmonary disease and obstructive sleep apnea syndrome[J]. Metabolomics, 2015, 11(6):1563-1574. doi: 10.1007/s11306-015-0808-5 URL
[34]	Tripathi A, Xu ZZ, Xue J, et al. Intermittent hypoxia and hypercapnia reproducibly change the gut microbiome and metabolome across rodent model systems[J]. mSystems, 2019, 4(2):e00058-19.
[35]	Zhang A, Sun H, Yan G, et al. Metabolomics for biomarker discovery: Moving to the clinic[J]. Biomed Res Int, 2015, 2015:354671.