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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (1): 1-5.doi: 10.6040/j.issn.1671-7554.0.2021.0275

• 基础医学 •    下一篇

硫化氢通过glutaredoxin-1调节氧化应激减轻急性阻塞性睡眠呼吸暂停诱发房颤的机制

黄辉宁1,2,杜娟娟2,孙燚2,侯应龙2,高梅1,2   

  1. 1.山东中医药大学第二临床医学院, 山东 济南 250001;2.山东第一医科大学第一附属医院心血管内科, 山东 济南 250014
  • 发布日期:2022-01-08
  • 通讯作者: 高梅. E-mail:gaomei0217@163.com
  • 基金资助:
    国家自然科学基金(81770334);山东省千佛山医院国家自然科学基金培育基金(QYPY2020NSFC1012)

Hydrogen sulfide alleviates acute obstructive sleep apnea-induced atrial fibrillation by regulating oxidative stress through glutaredoxin-1

HUANG Huining1,2, DU Juanjuan2, SUN Yi2, HOU Yinglong2, GAO Mei1,2   

  1. 1. The Second Clinical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China;
    2. Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, China
  • Published:2022-01-08

摘要: 目的 探讨硫化氢(H2S)减轻急性阻塞性睡眠呼吸暂停(OSA)诱发房颤的机制。 方法 硫氢化钠(NaHS)作为外源性H2S供体,8~10周龄健康成年雄性SD大鼠24只,体质量320~360 g,随机分为对照组、OSA诱发房颤组、NaHS+OSA组和氯化镉+NaHS+OSA组,每组6只。按照既往文献构建OSA诱发房颤模型,实验结束后处死大鼠,留取左心耳组织。采用免疫荧光、ELISA法检测左心耳谷氧还蛋白-1的表达水平;采用硫代巴比妥酸法检测左心耳丙二醛(MDA)含量。 结果 与OSA组相比,NaHS+OSA组房颤诱发次数减少、房颤持续时间缩短(P<0.05);与对照组相比,OSA组左心耳谷氧还蛋白-1表达减少,MDA含量增加,应用NaHS后,NaHS+OSA组谷氧还蛋白-1表达水平较OSA组增加,MDA含量降低(P<0.01),在NaHS基础上应用谷氧还蛋白-1抑制剂氯化镉后,氯化镉+NaHS+OSA组MDA含量增加(P<0.01),H2S减轻OSA诱发房颤的作用消失。 结论 外源性H2S减轻急性OSA诱发房颤,可能是通过上调心肌细胞谷氧还蛋白-1表达从而减轻心肌细胞氧化应激。

关键词: 心房颤动, 阻塞性睡眠呼吸暂停, 硫化氢, 谷氧还蛋白-1, 氧化应激

Abstract: Objective To explore the mechanism of hydrogen sulfide(H2S)alleviating atrial fibrillation(AF)induced by acute obstructive sleep apnea(OSA). Methods Sodium hydrosulfide(NaHS)was used as exogenous H2S donor, and 24 healthy adult male SD rats(aged 8-10 weeks)weighing 320 g to 360g were randomly divided into control group, OSA-induced AF group, NaHS+OSA group and cadmium chloride+NaHS+OSA group, with 6 in each group. The model of AF induced by OSA was established according to previous literature. The rats were sacrificed and left atrial appendages were collected. The expression of glutaredoxin-1 was detected with immunofluorescence and ELISA, and the content of malondialdehyde(MDA)was detected with thiobarbituric acid. Results Compared with the OSA group, the NaHS+OSA group had decreased frequency of AF and shortened duration of AF(P<0.05). Compared with control group, the OSA group had decreased expression of glutaredoxin-1 but increased MDA content. After NaHS was used, the expression of glutaredoxin-1 increased but the MDA content decreased compared with the OSA group(P<0.01). After cadmium chloride was used, the MDA content increased(P<0.01), and the effect of H2S on alleviating OSA-induced AF disappeared. Conclusion Exogenous application of H2S alleviate acute OSA-induced AF by regulating oxidative stress through glutaredoxin-1.

Key words: Atrial fibrillation, Obstructive sleep apnea, Hydrogen sulfide, Glutaredoxin-1, Oxidative stress

中图分类号: 

  • R541.7
[1] Santhanakrishnan R, Wang N, Larson MG, et al. Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction [J]. Circulation, 2016, 133(5): 484-492.
[2] Adderley NJ, Nirantharakumar K, Marshall T. Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: retrospective cohort studies [J]. BMJ, 2018, 361:k1717. doi: 10.1136/bmj.k1717.
[3] Serpytis R, Navickaite A, Serpytiene E, et al. Impact of atrial fibrillation on cognitive function, psychological distress, quality of life, and impulsiveness [J]. Am J Med, 2018, 131(6): 703.
[4] Shantha G, Pelosi F, Morady F. Relationship between obstructive sleep apnoea and AF [J]. Arrhythm Electrophysiol Rev, 2019, 8(3):180-183.
[5] Linz B, Hohl M, Lang L, et al. Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model [J]. Heart Rhythm, 2021, 18(3): 455-464.
[6] Bazan V, Vicente I, Lozano L, et al. Previously undetected obstructive sleep apnea in patients with new-onset atrial fibrillation [J]. Am J Cardiol, 2021, 138:46-52. doi: 10.1016/j.amjcard.2020.09.058.
[7] Linz D, McEvoy RD, Cowie MR, et al. Associations of obstructive sleep apnea with atrial fibrillation and continuous positive airway pressure treatment: a review [J]. JAMA Cardiol, 2018, 3(6): 532-540.
[8] Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: pathophysiological mechanisms and therapeutic implications [J]. Int J Cardiol, 2017, 230: 293-300. doi: 10.1016/j.ijcard.2016.12.120.
[9] Antonopoulos AS, Goliopoulou A, Oikonomou E, et al. Redox state in atrial fibrillation pathogenesis and relevant therapeutic approaches [J]. Curr Med Chem, 2019, 26(5): 765-779.
[10] Donnarumma E, Trivedi RK, Lefer DJ. Protective actions of H2S in acute myocardial infarction and heart failure [J]. Compr Physiol, 2017, 7(2): 583-602.
[11] Pei J, Wang F, Pei S, et al. Hydrogen sulfide promotes cardiomyocyte proliferation and heart regeneration via ROS scavenging [J]. Oxid Med Cell Longev, 2020, 2020: 1412696. doi: 10.1155/2020/1412696.
[12] Gao M, Zhang L, Scherlag BJ, et al. Low-level vagosympathetic trunk stimulation inhibits atrial fibrillation in a rabbit model of obstructive sleep apnea [J]. Heart Rhythm, 2015, 12(4): 818-824.
[13] Iwasaki YK, Kato T, Xiong F, et al. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model [J]. J Am Coll Cardiol, 2014, 64(19): 2013-2023.
[14] Beltowski J. Synthesis, metabolism, and signaling mechanisms of hydrogen sulfide: an overview [J]. Methods Mol Biol, 2019, 2007: 1-8. doi: 10.1007/978-1-4939-9528-8_1.
[15] Kang SC, Sohn EH, Lee SR. Hydrogen sulfide as a potential alternative for the treatment of myocardial fibrosis [J]. Oxid Med Cell Longev, 2020, 2020: 4105382. doi: 10.1155/2020/4105382.
[16] 曾奇虎, 翁静飞, 李小林, 等. 外源性硫化氢对2型糖尿病大鼠心肌纤维化及TGF-β1/Smads信号通路的影响[J]. 中国免疫学杂志, 2020, 36(6): 653-657. ZENG Qihu, WENG Jingfei, LI Xiaolin, et al. Effects of exogenous hydrogen sulfide on myocardial fibrosis and TGF-β1 /Smads signaling pathway in type 2 diabetic rats [J]. Chinese Journal of Immunology, 2020, 36(6): 653-657.
[17] 武韧, 常贵全, 孙凤起, 等. 硫化氢对糖尿病心肌病的保护作用[J]. 心血管病学进展, 2021, 42(1): 52-55. WU Ren, CHANG Guiquan, SUN Fengqi, et al. Protective effect of hydrogen sulfide in diabetic cardiomyopathy [J]. Advances in Cardiovascular Diseases, 2021, 42(1): 52-55.
[18] Salloum FN. Hydrogen sulfide and cardioprotection-Mechanistic insights and clinical translatability [J]. Pharmacol Ther, 2015, 152: 11-7. doi: 10.1016/j.pharmthera. 2015.04.004.
[19] Liang YF, Zhang DD, Yu XJ, et al. Hydrogen sulfide in paraventricular nucleus attenuates blood pressure by regulating oxidative stress and inflammatory cytokines in high salt-induced hypertension [J]. Toxicol Lett, 2017, 270: 62-71. doi: 10.1016/j.toxlet.2017.02.004.
[20] Citi V, Piragine E, Testai L, et al. The role of hydrogen sulfide and H2S-donors in myocardial protection against ischemia/reperfusion injury [J]. Curr Med Chem, 2018, 25(34): 4380-4401.
[21] 徐明星, 刘文秀, 梁雨亭, 等. 硫化氢在心血管疾病中的研究进展[J]. 中国现代医学杂志, 2020, 30(21): 34-38. XU Mingxing, LIU Wenxiu, LIANG Yuting, et al. Recent research of H2S and autophagy in cardiovascular diseases [J]. China Journal of Modern Medicine, 2020, 30(21): 34-38.
[22] Watts M, Kolluru GK, Dherange P, et al. Decreased bioavailability of hydrogen sulfide links vascular endothelium and atrial remodeling in atrial fibrillation [J]. Redox Biol, 2021, 38:101817. doi: 10.1016/j.redox.2020.101817.
[23] Xue X, Ling X, Xi W, et al. Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway [J]. Mol Med Rep, 2020, 22(3): 1759-1766.
[24] Cofta S, Winiarska HM, Plociniczak A, et al. Oxidative stress markers and severity of obstructive sleep apnea [J]. Adv Exp Med Biol, 2019, 1222:27-35. doi: 10.1007/5584_2019_433.
[25] 李春兰, 裴丽娟, 侯鹏. 心房颤动相关的生物学标记物 [J]. 中国心血管杂志, 2020, 25(4):397-400.
[26] Sanderson JE, Fang F, Lu M, et al. Obstructive sleep apnoea, intermittent hypoxia and heart failure with a preserved ejection fraction [J]. Heart, 2021, 107(3):190-194.
[27] Samman Tahhan A, Sandesara PB, Hayek SS, et al. Association between oxidative stress and atrial fibrillation [J]. Heart Rhythm, 2017, 14(12):1849-1855.
[28] Karam BS, Chavez-Moreno A, Koh W, et al. Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes [J]. Cardiovasc Diabetol, 2017, 16(1):120. doi: 10.1186/s12933-017-0604-9.
[29] Liu T, Zhao H, Li J, et al. Rosiglitazone attenuates atrial structural remodeling and atrial fibrillation promotion in alloxan-induced diabetic rabbits [J]. Cardiovasc Ther, 2014, 32(4):178-183.
[30] Li JY, He Y, Ke HH, et al. Plasma oxidative stress and inflammatory biomarkers are associated with the sizes of the left atrium and pulmonary vein in atrial fibrillation patients [J]. Clin Cardiol, 2017, 40(2):89-94.
[31] Burns M, Rizvi SHM, Tsukahara Y, et al. Role of glutaredoxin-1 and glutathionylation in cardiovascular diseases [J]. Int J Mol Sci, 2020, 21(18). doi: 10.3390/ijms21186803.
[32] Matsui R, Ferran B, Oh A, et al. Redox regulation via glutaredoxin-1 and protein s-glutathionylation [J]. Antioxid Redox Signal, 2020, 32(10):677-700.
[33] Han J, Weisbrod RM, Shao D, et al. The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells [J]. Redox Biol, 2016, 9:306-19. doi: 10.1016/j.redox.2016.09.003.
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