阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是一种呼吸性睡眠障碍,主要表现为睡眠时,上呼吸道有时被部分,有时被完全阻塞,并且反复发生的夜间打鼾,白天困倦,甚至有时出现夜间憋醒等情况,引起低通气或者呼吸暂停等症状。在低通气或呼吸暂停事件中,肺泡通气不良导致动脉血氧饱和度(SaO2)降低和二氧化碳动脉分压(PaCO2)逐渐升高,从而引起一系列并发症,如:高血压、胰岛素抵抗、冠心病等多器官、多系统损伤。此间歇性缺氧必然引起机体免疫功能及多种炎症指标发生改变,本文就OSAHS患者免疫及炎症指标做出综述,以增加对OSAHS免疫的了解,提高对OSAHS重视。
Sleep apnea-hypopnea syndrome (OSAHS) is a respiratory sleep disorder, which is mainly mani-fested by partially or completely blocked upper respiratory tract during sleep, recurring nocturnal snoring, daytime sleepiness, and sometimes even nocturnal awakening, causing symptoms such as hypopnea or apnea. In hypopnea or apnea events, poor alveolar ventilation leads to decreased arte-rial oxygen saturation (SaO2) and a gradual increase in arterial partial pressure (PaCO2) of carbon dioxide, resulting in a series of complications such as hypertension, insulin resistance, coronary heart disease and other multi-organ and multi-system injuries. This intermittent hypoxia will inev-itably cause changes in the body’s immune function and a variety of inflammatory indicators. This paper reviews the immune and inflammatory indicators of OSAHS patients to increase the under-standing of OSAHS immunity and improve the attention to OSAHS.
Sleep apnea-hypopnea syndrome (OSAHS) is a respiratory sleep disorder, which is mainly manifested by partially or completely blocked upper respiratory tract during sleep, recurring nocturnal snoring, daytime sleepiness, and sometimes even nocturnal awakening, causing symptoms such as hypopnea or apnea. In hypopnea or apnea events, poor alveolar ventilation leads to decreased arterial oxygen saturation (SaO2) and a gradual increase in arterial partial pressure (PaCO2) of carbon dioxide, resulting in a series of complications such as hypertension, insulin resistance, coronary heart disease and other multi-organ and multi-system injuries. This intermittent hypoxia will inevitably cause changes in the body’s immune function and a variety of inflammatory indicators. This paper reviews the immune and inflammatory indicators of OSAHS patients to increase the understanding of OSAHS immunity and improve the attention to OSAHS.
姜新新,冯恩志. 阻塞性睡眠呼吸暂停低通气综合征免疫功能的研究进展Advances in the Study of Immune Function in Obstructive Sleep Apnea-Hypopnea Syndrome[J]. 临床医学进展, 2022, 12(06): 5627-5632. https://doi.org/10.12677/ACM.2022.126814
参考文献ReferencesWolf, J., Rose-John, S. and Garbers, C. (2014) Interleukin-6 and Its Receptors: A Highly Regulated and Dynamic Sys-tem. Cytokine, 70, 11-20. <br>https://doi.org/10.1016/j.cyto.2014.05.024Poroyko, V.A., Carreras, A., Khalyfa, A., Khalyfa, A.A., Leone, V., Peris, E., Almendros, I., Gileles-Hillel, A., Qiao, Z., Hubert, N., et al. (2016) Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice. Scientific Reports, 6, Article No. 35405. <br>https://doi.org/10.1038/srep35405Lee, W.Y., Allison, M.A., Kim, D.J., Song, C.H. and Barrett-Connor, E. (2007) Association of Interleukin-6 and C-Reactive Protein with Subclinical Carotid Atherosclerosis (The Rancho Bernardo Study). American Journal of Cardiology, 99, 99-102. <br>https://doi.org/10.1016/j.amjcard.2006.07.070Esteve, E., Castro, A., López-Bermejo, A., Vendrell, J., Ricart, W. and Fernández-Real, J.M. (2007) Serum Interleukin-6 Correlates with Endothelial Dysfunction in Healthy Men Inde-pendently of Insulin Sensitivity. Diabetes Care, 30, 939-945. <br>https://doi.org/10.2337/dc06-1793Schaefer, E., Wu, W., Mark, C., Yang, A., DiGiacomo, E., Carlton-Smith, C., Salloum, S., Brisac, C., Lin, W., Corey, K.E., et al. (2017) Intermittent Hypoxia Is a Proinflammatory Stimulus Resulting in IL-6 Expression and M1 Macrophage Polariza-tion. Hepatology Communications, 1, 326-337. <br>https://doi.org/10.1002/hep4.1045Li, Y., Vgontzas, A.N., Fernandez-Mendoza, J., Kritikou, I., Basta, M., Pejovic, S., Gaines, J. and Bixler, E.O. (2017) Objective, But Not Sub-jective, Sleepiness Is Associated with Inflammation in Sleep Apnea. Sleep, 40, zsw033.
<br>https://doi.org/10.1093/sleep/zsw033Baessler, A., Nadeem, R., Harvey, M., Madbouly, E., Younus, A., Sajid, H., Naseem, J., Asif, A. and Bawaadam, H. (2013) Treatment for Sleep Apnea by Continuous Positive Airway Pressure Improves Levels of Inflammatory Markers—A Meta-Analysis. Journal of Inflammation, 10, Article No. 13. <br>https://doi.org/10.1186/1476-9255-10-13Van Eyck, A., Van Hoorenbeeck, K., De Winter, B.Y., Van Gaal, L., De Backer, W. and Verhulst, S.L. (2017) Sleep-Disordered Breathing, Systemic Adipokine Secretion, and Metabolic Dysregulation in Overweight and Obese Children and Adolescents. Sleep Medicine, 30, 52-56. <br>https://doi.org/10.1016/j.sleep.2015.11.014Smith, D.F., Hossain, M.M., Hura, A., Huang, G., McConnell, K., Ishman, S.L. and Amin, R.S. (2017) Inflammatory Milieu and Cardiovascular Homeostasis in Children with Obstructive Sleep Apnea. Sleep, 40, zsx022.
<br>https://doi.org/10.1093/sleep/zsx022Gaines, J., Vgontzas, A.N., Fernandez-Mendoza, J., Calhoun, S.L., He, F., Liao, D., Sawyer, M.D. and Bixler, E.O. (2016) Inflammation Mediates the Association Between Visceral Adiposity and Obstructive Sleep Apnea in Adolescents. American Journal of Physiology: Endocrinology and Metabolism, 311, E851-E858.
<br>https://doi.org/10.1152/ajpendo.00249.2016Kaditis, A.G., Gozal, D., Khalyfa, A., Kheirandish-Gozal, L., Capdevila, O.S., Gourgoulianis, K., Alexopoulos, E.I., Chaidas, K., Bhattacharjee, R., Kim, J., et al. (2014) Variants in C-Reactive Protein and IL-6 Genes and Susceptibility to Obstructive Sleep Apnea in Children: A Candidate-Gene Asso-ciation Study in European American and Southeast European Populations. Sleep Medicine, 15, 228-235. <br>https://doi.org/10.1016/j.sleep.2013.08.795Zhong, A., Xiong, X., Shi, M. and Xu, H. (2016) Roles of Inter-leukin (IL)-6 Gene Polymorphisms, Serum IL-6 Levels, and Treatment in Obstructive Sleep Apnea: A Meta-Analysis. Sleep and Breathing, 20, 719-731.
<br>https://doi.org/10.1007/s11325-015-1288-6Kong, D., Qin, Z., Wang, W. and Kang, J. (2017) Effect of Ob-structive Sleep Apnea on Carotid Artery Intima Media Thickness Related To Inflammation. Clinical and Investigative Medicine, 40, E25-E33.
<br>https://doi.org/10.25011/cim.v40i1.28051Rockstrom, M.D., Chen, L., Taishi, P., Nguyen, J.T., Gibbons, C.M., Veasey, S.C. and Krueger, J.M. (2018) Tumor Necrosis Factor Alpha in Sleep Regulation. Sleep Medicine Reviews, 40, 69-78.
<br>https://doi.org/10.1016/j.smrv.2017.10.005Krueger, J.M. and Opp, M.R. (2016) Sleep and Microbes. Inter-national Review of Neurobiology, 131, 207-225.
<br>https://doi.org/10.1016/bs.irn.2016.07.003Jewett, K.A., Taishi, P., Sengupta, P., Roy, S., Davis, C.J. and Krueger, J.M. (2015) Tumor Necrosis Factor Enhances the Sleep-Like State and Electrical Stimulation Induces a Wake-Like State in Co-Cultures of Neurons and Glia. European Journal of Neuroscience, 42, 2078-2090. <br>https://doi.org/10.1111/ejn.12968De Araújo Freitas, I.G., De Bruin, P.F., Bittencourt, L., De Bruin, V.M. and Tufik, S. (2015) What Can Blood Biomarkers Tell Us about Cardiovascular Risk in Obstructive Sleep Apnea? Sleep and Breathing, 19, 755-768.
<br>https://doi.org/10.1007/s11325-015-1143-9Ramesh, V., Thatte, H.S., McCarley, R.W. and Basheer, R. (2007) Adenosine and Sleep Deprivation Promote NF-κB Nuclear Translocation in Cholinergic Basal Forebrain. Journal of Neurochemistry, 100, 1351-1363.
<br>https://doi.org/10.1111/j.1471-4159.2006.04314.xKaushal, N., Ramesh, V. and Gozal, D. (2012) TNF-α and Temporal Changes in Sleep Architecture in Mice Exposed To Sleep Fragmentation. PLOS ONE, 7, Article ID: e45610. <br>https://doi.org/10.1371/journal.pone.0045610Ramesh, V., Nair, D., Zhang, S.X., Hakim, F., Kaushal, N., Kayali, F., Wang, Y., Li, R.C., Carreras, A. and Gozal, D. (2012) Disrupted Sleep without Sleep Curtailment Induces Sleepiness and Cognitive Dysfunction via the Tumor Necrosis Factor-α Pathway. Journal of Neuroinflammation, 9, Ar-ticle No. 91. <br>https://doi.org/10.1186/1742-2094-9-91He, K. and Kapur, V.K. (2017) Sleep-Disordered Breathing and Excessive Daytime Sleepiness. Sleep Medicine Clinics, 12, 369-382. <br>https://doi.org/10.1016/j.jsmc.2017.03.010Gozal, D. and Kheirandish-Gozal, L. (2009) Obesity and Excessive Daytime Sleepiness in Prepubertal Children with Obstructive Sleep Apnea. Pediatrics, 123, 13-18. <br>https://doi.org/10.1542/peds.2008-0228Tauman, R., O’Brien, L.M., Holbrook, C.R. and Gozal, D. (2004) Sleep Pressure Score: A New Index of Sleep Disruption in Snoring Children. Sleep, 27, 274-278. <br>https://doi.org/10.1093/sleep/27.2.274Song, D., Fang, G., Mao, S.Z., Ye, X., Liu, G., Gong, Y. and Liu, S.F. (2012) Chronic Intermittent Hypoxia Induces Atherosclerosis by NF-κB-Dependent Mechanisms. Biochimica et Bio-physica Acta (BBA)—Molecular Basis of Disease, 1822, 1650-1659. <br>https://doi.org/10.1016/j.bbadis.2012.07.010Reid, M.B., Lannergren, J. and Westerblad, H. (2002) Respira-tory and Limb Muscle Weakness Induced by Tumor Necrosis Factor-Alpha: Involvement of Muscle Myofilaments. American Journal of Respiratory and Critical Care Medicine, 166, 479-484. <br>https://doi.org/10.1164/rccm.2202005Wilcox, P., Milliken, C. and Bressler, B. (1996) High-Dose Tumor Ne-crosis Factor Alpha Produces an Impairment of Hamster Diaphragm Contractility. Attenuation with a Prostaglandin In-hibitor. American Journal of Respiratory and Critical Care Medicine, 153, 1611-1615. <br>https://doi.org/10.1164/ajrccm.153.5.8630610Shoham, S., Davenne, D., Cady, A.B., Dinarello, C.A. and Krueger, J.M. (1987) Recombinant Tumor Necrosis Factor and Interleukin 1 Enhance Slow-Wave Sleep. American Journal of Physiology, 253, R142-R149.
<br>https://doi.org/10.1152/ajpregu.1987.253.1.R142Nadeem, R., Molnar, J., Madbouly, E.M., Nida, M., Ag-garwal, S., Sajid, H., Naseem, J. and Loomba, R. (2013) Serum Inflammatory Markers in Obstructive Sleep Apnea: A Meta-Analysis. Journal of Clinical Sleep Medicine, 89, 1003-1012.
<br>https://doi.org/10.5664/jcsm.3070Kheirandish-Gozal, L. and Gozar, D. (2019) Obstructive Sleep Apnea and Inflammation:Proof of Concept Based on Two Illustrative Cytokines. International Journal of Molecular Sciences, 20, Article No. 459.
<br>https://doi.org/10.3390/ijms20030459黄磊, 徐爱晖. 阻塞性睡眠呼吸暂停综合征免疫网络的研究进展[J]. 临床肺科杂志, 2009, 14(3): 351-352.Xie, H., Yin, J., Bai, Y., Peng, H., Zhou, X. and Bai, J. (2019) Differ-ential Expression of Immune Markers in the Patients with Obstructive Sleep Apnea/hypopnea Syndrome. European Ar-chives of Oto-Rhino-Laryngology, 276, 735-744.
<br>https://doi.org/10.1007/s00405-018-5219-6Domagała-Kulawik, J., Osinska, I., Piechuta, A., Bielicki, P. and Skirecki, T. (2015) T, B, and NKT Cells in Systemic Inflammation in Obstructive Sleep Apnoea. Mediators of Inflamma-tion, 2015, Article ID: 161579.
<br>https://doi.org/10.1155/2015/161579计明, 李从荣. 阻塞性睡眠呼吸暂停综合征患者血清IL-6、TNF-α测定的临床意义[J]. 微循环学杂志, 2008, 18(4): 43-45.Kivanc, T., Kulaksizoglu, S., Lakadamyali, H. and Eyuboglu, F. (2018) Importance of Laboratory Parameters in Patients with Obstructive Sleep Apnea and Their Relation-ship with Cardiovascular Diseases. Journal of Clinical Laboratory Analysis, 32, e22199. <br>https://doi.org/10.1002/jcla.22199Al-Halawani, M., Kyung, C., Liang, F., Kaplan, I., Moon, J., Clerger, G., et al. (2020) Treatment of Obstructive Sleep Apnea with CPAP Improves Chronic Inflammation Measured by Neutro-phil-To-Lymphocyte Ratio. Journal of Clinical Sleep Medicine, 16, 251-257. <br>https://doi.org/10.5664/jcsm.8176Ermakov, A.V., Konkova, M.S., Kostyuk, S.V., Izevskaya, V.L., Baranova, A. and Veiko, N.N. (2013) Oxidised Extracellular DNA as a Stress Signal in Human Cells. Oxidative Medicine and Cel-lular Longevityv, 2013, Article ID: 649747. <br>https://doi.org/10.1155/2013/649747Lo, Y.M., Tein, M.S., Lau, T.K., Haines, C.J., Leung, T.N., Poon, P.M., Wainscoat, J.S., Johnson, P.J., Chang, A.M. and Hjelm, N.M. (1998) Quantitative Analysis of Fetal DNA in Maternal Plasma and Serum: Implications for Noninvasive Prenatal Diagnosis. The American Journal of Human Genetics, 62, 768-775. <br>https://doi.org/10.1086/301800Yokoe, T., Minogu-chi, K., Matsuo, H., Oda, N., Minoguchi, H., Yoshino, G., Hirano, T. and Adachi, M. (2003) Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients with Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Con-tinuous Positive Airway Pressure. Circulation, 107, 1129-1134.
<br>https://doi.org/10.1161/01.CIR.0000052627.99976.18韩林华, 刘晨, 王红阳, 张盼盼, 王立民, 黄艳, 孟晓华. 持续气道正压通气对睡眠呼吸暂停患者疗效及C-反应蛋白和血沉的影响[J]. 中国耳鼻咽喉头颈外科, 2013, 20(6): 331-332.陈艺慧, 闵丽, 张海涛, 努尔艾力•依米提. 睡眠呼吸暂停低通气综合征患者CRP、PCT水平的分析[J]. 兵团医学, 2016, 50(4): 33-34.