阻塞性睡眠呼吸暂停对非酒精性脂肪性肝病的影响

许青青; 唐海英; 毛靖伟

doi:10.3969/j.issn.1001-5256.2021.01.042

阻塞性睡眠呼吸暂停对非酒精性脂肪性肝病的影响

DOI: 10.3969/j.issn.1001-5256.2021.01.042

a.
大连医科大学附属第一医院消化内科，辽宁大连 116011
b.
大连医科大学附属第一医院呼吸睡眠诊疗中心，辽宁大连 116011

基金项目:

国家自然科学基金资助项目 (81500402)

作者贡献声明：许青青负责资料分析，撰写论文；唐海英参与资料分析，修改论文；毛靖伟负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
许青青(1993—)，女，主要从事非酒精性脂肪性肝病临床及基础研

通信作者:
毛靖伟，jingweimao@163.com

中图分类号: R575.5; R56
计量
- 文章访问数: 504
- HTML全文浏览量: 241
- PDF下载量: 40
- 被引次数: 0
出版历程
- 收稿日期: 2020-07-06
- 录用日期: 2020-08-26
- 出版日期: 2021-01-20

Impact of obstructive sleep apnea on nonalcoholic fatty liver disease

a.
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China
b.
Respiratory and Sleep Clinic, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China

摘要

摘要: 阻塞性睡眠呼吸暂停(OSA)引起机体长期处于慢性间歇性缺氧可导致多系统、多器官病变，严重者可发生心源性猝死。除合并呼吸、心脑血管、内分泌代谢等疾病外，OSA与消化系统疾病中的非酒精性脂肪性肝病(NAFLD)也有密切关联。简述了OSA和NAFLD的现状，叙述了OSA对NAFLD的影响，归纳了OSA影响NAFLD的机制，提出通过探索OSA影响NAFLD的可能机制，从OSA角度为NAFLD寻找新的潜在防治靶点，对延缓、甚至阻断NAFLD进展具有重要意义。
- 睡眠呼吸暂停, 阻塞性 /
- 非酒精性脂肪性肝病 /
- 低氧
Abstract: Obstructive sleep apnea (OSA) may induce chronic intermittent hypoxia, which may lead to the disorders of multiple systems and organs and even sudden cardiac death in severe cases. Besides respiratory, cardiovascular, endocrine, and metabolic diseases, OSA is also closely associated with nonalcoholic fatty liver disease (NAFLD). This article briefly describes the current status of OSA and NAFLD, introduces the impact of OSA on NAFLD, and reviews the mechanisms of OSA in NAFLD. It is pointed out that clarifying the mechanisms of OSA in affecting NAFLD and discovering potential prevention and treatment targets for NAFLD from the aspect of OSA are of great significance in delaying and even blocking the progression of NAFLD.
- Sleep Apnea, Obstructive /
- Non-alcoholic Fatty Liver Disease /
- Hypoxia

HTML全文

参考文献(49)

[1]	ESLAM M, VALENTI L, ROMEO S. Genetics and epigenetics of NAFLD and NASH: Clinical impact[J]. J Hepatol, 2018, 68(2): 268-279. DOI: 10.1016/j.jhep.2017.09.003
[2]	COTTER TG, RINELLA M. Nonalcoholic fatty liver disease 2020: The state of the disease[J]. Gastroenterology, 2020, 158(7): 1851-1864. DOI: 10.1053/j.gastro.2020.01.052
[3]	ZHOU J, ZHOU F, WANG W, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71(5): 1851-1864. DOI: 10.1002/hep.31150
[4]	SHIMA T, SEKI K, UMEMURA A, et al. Influence of lifestyle-related diseases and age on the development and progression of non-alcoholic fatty liver disease[J]. Hepatol Res, 2015, 45(5): 548-559. DOI: 10.1111/hepr.12384
[5]	JORDAN AS, MCSHARRY DG, MALHOTRA A. Adult obstructive sleep apnoea[J]. Lancet, 2014, 383(9918): 736-747. DOI: 10.1016/S0140-6736(13)60734-5
[6]	BIN-HASAN S, KATZ S, NUGENT Z, et al. Prevalence of obstructive sleep apnea among obese toddlers and preschool children[J]. Sleep Breath, 2018, 22(2): 511-515. DOI: 10.1007/s11325-017-1576-4
[7]	SARKAR P, MUKHERJEE S, CHAI-COETZER CL, et al. The epidemiology of obstructive sleep apnoea and cardiovascular disease[J]. J Thorac Dis, 2018, 10(Suppl 34): s4189-s4200.
[8]	GAINES J, VGONTZAS AN, FERNANDEZ-MENDOZA J, et al. Obstructive sleep apnea and the metabolic syndrome: The road to clinically-meaningful phenotyping, improved prognosis, and personalized treatment[J]. Sleep Med Rev, 2018, 42: 211-219. DOI: 10.1016/j.smrv.2018.08.009
[9]	JELENIK T, KAUL K, SÉQUARIS G, et al. Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver[J]. Diabetes, 2017, 66(8): 2241-2253. DOI: 10.2337/db16-1147
[10]	MESARWI OA, LOOMBA R, MALHOTRA A. Obstructive sleep apnea, hypoxia, and nonalcoholic fatty liver disease[J]. Am J Respir Crit Care Med, 2019, 199(7): 830-841. DOI: 10.1164/rccm.201806-1109TR
[11]	ASFARI MM, NIYAZI F, LOPEZ R, et al. The association of nonalcoholic steatohepatitis and obstructive sleep apnea[J]. Eur J Gastroenterol Hepatol, 2017, 29(12): 1380-1384. DOI: 10.1097/MEG.0000000000000973
[12]	ARISOY A, SERTOČULLARINDAN B, EKIN S, et al. Sleep apnea and fatty liver are coupled via energy metabolism[J]. Med Sci Monit, 2016, 22: 908-913. DOI: 10.12659/MSM.898214
[13]	CAKMAK E, DUKSAL F, ALTINKAYA E, et al. Association between the severity of nocturnal hypoxia in obstructive sleep apnea and non-alcoholic fatty liver damage[J]. Hepat Mon, 2015, 15(11): e32655.
[14]	JIN S, JIANG S, HU A. Association between obstructive sleep apnea and non-alcoholic fatty liver disease: A systematic review and meta-analysis[J]. Sleep Breath, 2018, 22(3): 841-851. DOI: 10.1007/s11325-018-1625-7
[15]	SOOKOIAN S, PIROLA CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: A meta-analysis[J]. Obes Surg, 2013, 23(11): 1815-1825. DOI: 10.1007/s11695-013-0981-4
[16]	NOBILI V, CUTRERA R, LICCARDO D, et al. Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of obesity/insulin resistance[J]. Am J Respir Crit Care Med, 2014, 189(1): 66-76.
[17]	PETTA S, MARRONE O, TORRES D, et al. Obstructive sleep apnea is associated with liver damage and atherosclerosis in patients with non-alcoholic fatty liver disease[J]. PLoS One, 2015, 10(12): e0142210. DOI: 10.1371/journal.pone.0142210
[18]	PASCHETTA E, BELCI P, ALISI A, et al. OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease[J]. Mediators Inflamm, 2015, 2015: 815721.
[19]	FENG SZ, TIAN JL, ZHANG Q, et al. An experimental research on chronic intermittent hypoxia leading to liver injury[J]. Sleep Breath, 2011, 15(3): 493-502. DOI: 10.1007/s11325-010-0370-3
[20]	SHERWANI SI, ALDANA C, USMANI S, et al. Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus[J]. Sleep, 2013, 36(12): 1849-1858. DOI: 10.5665/sleep.3214
[21]	FANG Y, ZHANG Q, TAN J, et al. Intermittent hypoxia-induced rat pancreatic β-cell apoptosis and protective effects of antioxidant intervention[J]. Nutr Diabetes, 2014, 4: e131. DOI: 10.1038/nutd.2014.28
[22]	DRAGER LF, LI J, SHIN MK, et al. Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea[J]. Eur Heart J, 2012, 33(6): 783-790. DOI: 10.1093/eurheartj/ehr097
[23]	SEMENZA GL. Oxygen sensing, homeostasis, and disease[J]. N Engl J Med, 2011, 365(6): 537-547. DOI: 10.1056/NEJMra1011165
[24]	MESARWI OA, SHIN MK, DRAGER LF, et al. Lysyl oxidase as a serum biomarker of liver fibrosis in patients with severe obesity and obstructive sleep apnea[J]. Sleep, 2015, 38(10): 1583-1591. DOI: 10.5665/sleep.5052
[25]	NADEEM R, SINGH M, NIDA M, et al. Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: A meta-regression analysis[J]. J Clin Sleep Med, 2014, 10(5): 475-489. DOI: 10.5664/jcsm.3690
[26]	LI J, THORNE LN, PUNJABI NM, et al. Intermittent hypoxia induces hyperlipidemia in lean mice[J]. Circ Res, 2005, 97(7): 698-706. DOI: 10.1161/01.RES.0000183879.60089.a9
[27]	PARIKH MP, GUPTA NM, MCCULLOUGH AJ. Obstructive sleep apnea and the liver[J]. Clin Liver Dis, 2019, 23(2): 363-382. DOI: 10.1016/j.cld.2019.01.001
[28]	BARROS D, GARCÍA-RÍO F. Obstructive sleep apnea and dyslipidemia: From animal models to clinical evidence[J]. Sleep, 2019, 42(3): zsy236.
[29]	KIM SY, JEONG JM, KIM SJ, et al. Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex[J]. Nat Commun, 2017, 8(1): 2247. DOI: 10.1038/s41467-017-02325-2
[30]	SUNDARAM SS, HALBOWER A, PAN Z, et al. Nocturnal hypoxia-induced oxidative stress promotes progression of pediatric non-alcoholic fatty liver disease[J]. J Hepatol, 2016, 65(3): 560-569. DOI: 10.1016/j.jhep.2016.04.010
[31]	CHEN LD, WU RH, HUANG YZ, et al. The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats[J]. Sleep Breath, 2020, 24(4): 1767-1773. DOI: 10.1007/s11325-020-02091-4
[32]	ALSHAMMARI GM, BALAKRISHNAN A, CHINNASAMY T. Butein protects the nonalcoholic fatty liver through mitochondrial reactive oxygen species attenuation in rats[J]. Biofactors, 2018, 44(3): 289-298. DOI: 10.1002/biof.1428
[33]	KUMAR D, DWIVEDI DK, LAHKAR M, et al. Hepatoprotective potential of 7, 8-Dihydroxyflavone against alcohol and high-fat diet induced liver toxicity via attenuation of oxido-nitrosative stress and NF-κB activation[J]. Pharmacol Rep, 2019, 71(6): 1235-1243. DOI: 10.1016/j.pharep.2019.07.002
[34]	KANG HH, KIM IK, LEE HI, et al. Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4/MyD88/MAPK/NF-kB signaling pathways[J]. Biochem Biophys Res Commun, 2017, 490(2): 349-355. DOI: 10.1016/j.bbrc.2017.06.047
[35]	RAO J, QIAN X, WANG P, et al. All-trans retinoic acid preconditioning protects against liver ischemia/reperfusion injury by inhibiting the nuclear factor kappa B signaling pathway[J]. J Surg Res, 2013, 180(2): e99-e106. DOI: 10.1016/j.jss.2012.04.008
[36]	REINKE C, BEVANS-FONTI S, DRAGER LF, et al. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes[J]. J Appl Physiol (1985), 2011, 111(3): 881-890. DOI: 10.1152/japplphysiol.00492.2011
[37]	REGUEIRA T, LEPPER PM, BRANDT S, et al. Hypoxia inducible factor-1 alpha induction by tumour necrosis factor-alpha, but not by toll-like receptor agonists, modulates cellular respiration in cultured human hepatocytes[J]. Liver Int, 2009, 29(10): 1582-1592. DOI: 10.1111/j.1478-3231.2009.02109.x
[38]	NOBILI V, ALISI A, CUTRERA R, et al. Altered gut-liver axis and hepatic adiponectin expression in OSAS: Novel mediators of liver injury in paediatric non-alcoholic fatty liver[J]. Thorax, 2015, 70(8): 769-781. DOI: 10.1136/thoraxjnl-2015-206782
[39]	BARCELÓ A, ESQUINAS C, ROBLES J, et al. Gut epithelial barrier markers in patients with obstructive sleep apnea[J]. Sleep Med, 2016, 26: 12-15. DOI: 10.1016/j.sleep.2016.01.019
[40]	SAFARI Z, GÉRARD P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)[J]. Cell Mol Life Sci, 2019, 76(8): 1541-1558.
[41]	MASHAQI S, GOZAL D. Obstructive sleep apnea and systemic hypertension: Gut dysbiosis as the mediator?[J]. J Clin Sleep Med, 2019, 15(10): 1517-1527. DOI: 10.5664/jcsm.7990
[42]	KIM CW, YUN KE, JUNG HS, et al. Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses[J]. J Hepatol, 2013, 59(2): 351-357. DOI: 10.1016/j.jhep.2013.03.035
[43]	PERELIS M, RAMSEY KM, MARCHEVA B, et al. Circadian transcription from beta cell function to diabetes pathophysiology[J]. J Biol Rhythms, 2016, 31(4): 323-336. DOI: 10.1177/0748730416656949
[44]	SHIGIYAMA F, KUMASHIRO N, TSUNEOKA Y, et al. Mechanisms of sleep deprivation-induced hepatic steatosis and insulin resistance in mice[J]. Am J Physiol Endocrinol Metab, 2018, 15(5): 848-858.
[45]	GAO T, WANG ZX, CAO J, et al. Melatonin attenuates microbiota dysbiosis of jejunum in short-term sleep deprived mice[J]. J Microbiol, 2020, 58(7): 588-597. DOI: 10.1007/s12275-020-0094-4
[46]	PATIL SP, AYAPPA IA, CAPLES SM, et al. Treatment of adult obstructive sleep apnea with positive airway pressure: An American Academy of Sleep Medicine Clinical Practice Guideline[J]. J Clin Sleep Med, 2019, 15(2): 335-343. DOI: 10.5664/jcsm.7640
[47]	LIU X, MIAO Y, WU F, et al. Effect of CPAP therapy on liver disease in patients with OSA: A review[J]. Sleep Breath, 2018, 22(4): 963-972. DOI: 10.1007/s11325-018-1622-x
[48]	UMBRO I, FABIANI V, FABIANI M, et al. Association between non-alcoholic fatty liver diseases and obstructive apnea[J]. Word J Gastroenterol, 2020, 26(20): 2669-2681. DOI: 10.3748/wjg.v26.i20.2669
[49]	KIM D, AHMED A, KUSHIDA C. Continuous positive airway pressure therapy on nonalcoholic fatty liver disease in patients with obstructive sleep apnea[J]. J Clin Sleep Med, 2018, 14(8): 1315-1322. DOI: 10.5664/jcsm.7262