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吸入低浓度氢气对小鼠哮喘和睡眠功能的影响

赵悦 魏璐 张学伟 朱丽 杜俊蓉

赵悦, 魏璐, 张学伟, 等. 吸入低浓度氢气对小鼠哮喘和睡眠功能的影响[J]. 四川大学学报(医学版), 2020, 51(2): 219-224. doi: 10.12182/20200360103
引用本文: 赵悦, 魏璐, 张学伟, 等. 吸入低浓度氢气对小鼠哮喘和睡眠功能的影响[J]. 四川大学学报(医学版), 2020, 51(2): 219-224. doi: 10.12182/20200360103
ZHAO Yue, WEI Lu, ZHANG Xue-wei, et al. Effects of Low Concentration Hydrogen Inhalation on Asthma and Sleep Function in Mice[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2020, 51(2): 219-224. doi: 10.12182/20200360103
Citation: ZHAO Yue, WEI Lu, ZHANG Xue-wei, et al. Effects of Low Concentration Hydrogen Inhalation on Asthma and Sleep Function in Mice[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2020, 51(2): 219-224. doi: 10.12182/20200360103

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吸入低浓度氢气对小鼠哮喘和睡眠功能的影响

doi: 10.12182/20200360103
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    E-mail:dujr_1@163.com

Effects of Low Concentration Hydrogen Inhalation on Asthma and Sleep Function in Mice

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  • 摘要:   目的  探讨吸入低浓度氢气对小鼠哮喘和睡眠功能的影响及其潜在机制。  方法  在哮喘实验中,BALB/c小鼠随机分为正常对照组、哮喘模型组和氢气治疗组,卵清蛋白(ovalbumin,OVA)诱导建立哮喘模型后,氢气治疗组每天吸入24~26 mL/L氢气,连续7 d,正常对照组和哮喘模型组在相同条件下吸入空气;ELISA法检测小鼠肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中白细胞介素(interleukin,IL)-4、IL-13和干扰素-γ(interferon-γ,IFN-γ)质量浓度;比色法检测肺组织中丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性;HE染色观察肺组织病理学改变。在睡眠实验中,ICR小鼠随机分为空白对照组,氢气治疗1 d、3 d、5 d组和地西泮组,观察吸入24~26 mL/L氢气对各组小鼠腹腔注射阈上剂量戊巴比妥钠所致小鼠睡眠时间以及阈下剂量所致小鼠睡眠发生率的影响。  结果  哮喘实验发现,与正常对照组比较,哮喘模型组小鼠BALF中IL-4、IL-13质量浓度均增加(P<0.05),IFN-γ质量浓度降低(P<0.001);肺组织中MDA含量增加(P<0.01),GSH含量降低(P<0.05),SOD活性轻度降低(P>0.05)。与哮喘模型组相比,氢气治疗组小鼠BALF中IL-4和IL-13质量浓度均降低、INF-γ质量浓度增加(P<0.05),而肺组织中MDA含量略降低(P>0.05),GSH含量和SOD活性增加(P<0.05)。HE染色结果显示氢气治疗可以减轻哮喘小鼠肺组织病理损伤。在睡眠实验中,腹腔注射阈上剂量戊巴比妥钠后,与空白对照组比较,各氢气治疗组小鼠睡眠潜伏期均缩短(P<0.05)、睡眠时间延长(P<0.001);同时各氢气治疗组小鼠睡眠潜伏期均长于地西泮组(P<0.001),睡眠时间短于地西泮组(P<0.001)。腹腔注射阈下剂量戊巴比妥钠后,与空白对照组比较,氢气吸入1 d和5 d睡眠发生率增加(P<0.01),与地西泮组比较差异均无统计学意义;氢气吸入3 d睡眠发生率轻度增加(P>0.05),其睡眠发生率低于地西泮组(P<0.05)。  结论  吸入低浓度氢气可以缓解OVA诱导的小鼠哮喘,其机制可能与氢气的抗氧化与抗炎作用有关。此外,吸入低浓度氢气对小鼠睡眠功能有一定改善作用。
  • 图  1  小鼠肺泡灌洗液中IL-4、IL-13、IFN-γ表达水平

    Figure  1.  The levels of IL-4, IL-13 and IFN-γ in bronchoalveolar lavage fluid of mice

    *P<0.05, ***P<0.001, vs. control group; #P< 0.05, ##P< 0.01, vs. model group

    图  2  小鼠肺组织中GSH、MDA含量和SOD活性

    Figure  2.  The levels of GSH and MDA and the activity of SOD in lung tissues of mice

    *P<0.05, **P<0.01, vs. control group; #P< 0.05, ##P< 0.01, vs. model group

    图  3  HE染色各组肺泡组织病理改变。×200

    Figure  3.  The alveolar pathological changes of the 3 groups assessed by HE staining. ×200

    A: Control group; B: Model group; C: Hydrogen group

    图  4  吸入低浓度氢气对阈上剂量戊巴比妥钠所致小鼠睡眠潜伏期和睡眠时间的影响

    Figure  4.  The effects of hydrogen inhalation on the sleep latency and duration induced by upper threshold dose of sodium pentobarbital in mice

    *P<0.05, ***P<0.001, vs. control group; ###P<0.001, vs. diazepam group;& P<0.05,vs. 1 d hydrogen group

  • [1] MISHRA V, BANGA J, SILVEYRA P. Oxidative stress and cellular pathways of asthma and inflammation: therapeutic strategies and pharmacological targets. Pharmacol Ther,2018,181: 169–182. doi: 10.1016/j.pharmthera.2017.08.011
    [2] OPINA M T, MOORE W C. Phenotype-driven therapeutics in severe asthma. Curr Allergy Asthma Rep, 2017, 17(2): 10[2019-08-14]. https://link.springer.com/article/10.1007%2Fs11882-017-0678-1. doi: 10.1007/s11882-017-0678-1.
    [3] IIDA A, NOSAKA N, YUMOTO T, et al. The clinical application of hydrogen as a medical treatment. Acta Med Okayama,2016,70(5): 331–337. doi: 10.18926/AMO/54590
    [4] 张宁, 张景熙. 吸人高浓度氢气对大鼠支气管哮喘的治疗作用. 国际呼吸杂志,2015,35(3): 179–182. doi: 10.3760/cma.j.issn.1673-436X.2015.03.005
    [5] HUANG P, WEI S, HUANG W, et al. Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model. Int Immunopharmacol, 2019, 74: 105646[2019-04-18]. https://doi.org/10.1016/j.intimp.2019.05.031.
    [6] 卢宏涛, 孙学军. 氢气医学研究的进展、争议和挑战. 第二军医大学学报,2018,39(11): 1181–1187. doi: 10.16781/j.0258-879x.2018.11.1181
    [7] KAVANAGH J, JACKSON D J, KENT B D. Sleep and asthma. Curr Opin Pulm Med,2018,24(6): 569–573. doi: 10.1097/MCP.0000000000000526
    [8] TAYLOR D J, PETERSON A L, PRUIKSMA K E, et al. Impact of cognitive behavioral therapy for insomnia disorder on sleep and comorbid symptoms in military personnel: a randomized clinical trial. Sleep, 2018, 41(6) [2019-08-14]. https://doi.org/10.1093/sleep/zsy069.
    [9] MATSUMOTO A, YAMAFUJI M, TACHIBANA T, et al. 'Oralhydrogen water' induces neuroprotective ghrelin secretion in mice. Sci Rep, 2013, 3: 3273[2019-08-14]. https://www.nature.com/articles/srep03273. doi: 10.1038/srep03273.
    [10] MIZUNO K, SASAKI A T, EBISU K, et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res,2017,7(4): 247–255. doi: 10.4103/2045-9912.222448
    [11] LECKER B, ILLI L, LEMMER A, et al. Biological hydrogen methanation—a review. Bioresour Technol,2017,245(Pt A): 1220–1228. doi: 10.1016/j.biortech.2017.08.176
    [12] MATEI N, CAMARA R, ZHANG J H. Emerging mechanisms and novel applications of hydrogen gas therapy. Med Gas Res,2018,8(3): 98–102. doi: 10.4103/2045-9912.239959
    [13] LI S, LIAO R, SHENG X, et al. Hydrogen gas in cancer treatment. Front Oncol, 2019, 9: 696[2019-08-14]. https://doi.org/10.3389/fonc.2019.00696.
    [14] HUANG C S, KAWAMURA T, TOYODA Y, et al. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res,2010,44(9): 971–982. doi: 10.3109/10715762.2010.500328
    [15] CHEN X, LI X, GU W, et al. LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction. Int Immunopharmacol,2017,44: 9–15. doi: 10.1016/j.intimp.2016.12.029
    [16] ROBINSON M J, PROUT M, MEARNS H, et al. IL-4 haploinsufficiency specifically impairs IgE responses against allergens in mice. J Immunol,2017,198(5): 1815–1822. doi: 10.4049/jimmunol.1601434
    [17] RAPHAEL I, NALAWADE S, EAGAR T N, et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine,2015,74(1): 5–17. doi: 10.1016/j.cyto.2014.09.011
    [18] SAHINER U M, BIRBEN E, ERZURUM S, et al. Oxidative stress in asthma: part of the puzzle. Pediatr Allergy Immunol,2018,29(8): 789–800. doi: 10.1111/pai.12965
    [19] COMHAIR S A, ERZURUM S C. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal,2010,12(1): 93–124. doi: 10.1089/ars.2008.2425
    [20] BEN A A, BEN N H, FETOUI H, et al. Alteration in systemic markers of oxidative and antioxidative status in Tunisian patients with asthma: relationships with clinical severity and airflow limitation. J Asthma,2016,53(3): 227–237. doi: 10.3109/02770903.2015.1087559
    [21] FERINI S L, GALBIATI A, COMBI R. Sleep disorder-related headaches. Neurol Sci,2019,40(Suppl 1): 107–113. doi: 10.1007/s10072-019-03837-z
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出版历程
  • 收稿日期:  2019-08-14
  • 修回日期:  2019-11-26
  • 刊出日期:  2020-03-01

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