In order to explore the effects of a combined exposure of formaldehyde (FA) and PM2.5 with low concentration on the asthmatic mice, 70male Balb/c mice were randomly divided into 5groups:control group, OVA group, FA + OVA group, PM2.5 + OVA group, FA + PM2.5 + OVA group. Amongst 14mice in each group, 6were tested for airway hyper reactivity (AHR), and the remaining 8were detected for T-IgE in serum, as well as IFN-γ, IL-4in BALF, and ROS, MDA in lung tissue. Besides, the inflammatory cells in BALF were counted. In addition, H&E staining and immunohistochemical analysis of p-p38MAPK and p-p65NF-κ B were conducted with mice lung. A significant increase in the level of MDA (P<0.001), as well as a trend of increase in inflammatory lung cells(P>0.05) were demonstrated in asthmatic mice group exposed to 0.5mg/m3 FA alone. While in the group exposed to combined 0.5mg/m3 FA and 0.5mg/kg PM2.5 with low concentration, a significant aggravation in lung inflammation(P<0.05, P<0.01) and attenuation in lung function(P<0.01) were observed. Significant increase was also found in the level of both oxidative stress and the phosphorylation of p38MAPK and NF-κ B in lung(P<0.05, P<0.001). In addition, the release of Th2 type cytokine was also enhanced significantly(P<0.01). Hence exposure to low-concentration FA alone could lead to the aggravation instead of inhibition of lung injury in asthmatic mice, and might further promote the damage to lungs in asthmatic mice caused by PM2.5. In conclusion, combined exposure to FA and PM2.5 with low concentration could lead to severe lung damage in asthmatic mice, with a possible correlation to the imbalance of Th1/Th2 type responses intensified by the ROS-mediated p38MAPK pathway.
鲁娴娴, 黄佳伟, 崔海燕, 吕柯, 赵元腾, 魏婷婷, 李贝贝, 卢浩楠, 李睿. 低浓度甲醛和PM2.5联合暴露对哮喘小鼠的影响[J]. 中国环境科学, 2020, 40(3): 1335-1344.
LU Xian-xian, HUANG Jia-wei, CUI Hai-yan, Lü Ke, ZHAO Yuan-teng, WEI Ting-ting, LI Bei-bei, LU Hao-nan, LI Rui. The effect of combined exposure of low concentration formaldehyde and PM2.5 on asthma model mice. CHINA ENVIRONMENTAL SCIENCECE, 2020, 40(3): 1335-1344.
Rumchev K B, Spickett J T, Bulsara M K, et al. Domestic exposure to formaldehyde significantly increases the risk of asthma in young children[J]. European Respiratory Journal, 2002,20(2):403-408.
[2]
岳伟,金晓滨,潘小川,等.室内甲醛与成人过敏性哮喘关系的研究[J]. 中国公共卫生, 2004,20(8):904-906. Yue W, Jin X B, Pan X C, et al. Study on the relationship between indoor formaldehyde and adult allergic asthma[J]. Chinese Public Health, 2004,20(8):904-906.
[3]
Liu D, Zheng Y, Li B, et al. Adjuvant effects of gaseous formaldehyde on the hyper-responsiveness and inflammation in a mouse asthma a model immunized by ovalbumin[J]. Journal of Immunotoxicology, 2011,8(4):305-314.
[4]
Ezratty V, Bonay M, Neukirch C, et al. Effect of Formaldehyde on Asthmatic Response to Inhaled Allergen Challenge[J]. Environmental Health Perspectives, 2007,115(2):210-214.
[5]
Li L L, Li H, He Y F, et al. Differential effects of formaldehyde exposure on airway inflammation and bronchial hyperresponsiveness in BALB/c and C57BL/6mice[J]. PLOS ONE, 2017,12(6):e0179231.
[6]
Sakai K, Yokoyama A, Kohno N, et al. Prolonged antigen exposure ameliorates airway inflammation but not remodeling in a mouse model of bronchial asthma[J]. International Archives of Allergy and Immunology, 2001,126(2):126-134.
[7]
Franco A L D S, Domingos H V, Damazo A S, et al. Reduced allergic lung inflammation in rats following formaldehyde exposure:Long-term effects on multiple effector systems[J]. Toxicology, 2009,256(3):157-163.
[8]
周骥, 孙庆华, 许建明, 等. 上海地区不同PM2.5污染过程对炎症应激影响的差异性[J]. 气象, 2018, 44(12):106-111. Zhou J, Sun Q H, Xu J M. The differences of the effects on inflammatory stress of different process of PM2.5 pollution in Shanghai[J]. Meteorology, 2018,44(12):106-111.
[9]
Riva D R, Magalhães C B, Lopes A A, et al. Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice[J]. Inhalation Toxicology, 2011,23(5):257.
[10]
Zhang X, Zhong W, Meng Q, et al. Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously sensitized mice[J]. Journal of Asthma Research, 2015,52(8):785-794.
[11]
Kim K H, Kabir E, Kabir S. A review on the human health impact of airborne particulate matter[J]. Environment International, 2015,74:136-143.
[12]
Mirabelli M C, Vaidyanathan A, Flanders W D, et al. Outdoor PM2.5, ambient air temperature, and asthma symptoms in the past 14 days among adults with active asthma[J]. Environmental Health Perspectives, 2016,124(12):1882-1890.
[13]
閤静,郭晴,江清英,等.甲醛复合PM2.5致小鼠血液毒性的研究[J]. 中国环境科学, 2017,37(7):2740-2748. Ge J, Guo Q, Jiang Q Y, et al. Study on hemotoxicity of mice induced by formaldehyde combined with PM2.5[J]. China Environmental Science, 2017,37(7):2740-2748.
[14]
Song J, Kang J, Lin B, et al. Mediating role of TRPV1I on channels in the co-exposure to PM2.5 and formaldehyde of balb/c mice asthma model[J]. Scientific Reports, 2017,7(1):11926.
[15]
梁晓军,施健,赵萍,等.中国居民室内甲醛暴露水平及健康效应研究进展[J]. 环境卫生学杂志, 2017,7(2):170-181. Liang X J, Shi J, Zhao P, et al. Advances in research on indoor formaldehyde exposure level and health effects in Chinese residents[J]. Journal of Environmental Hygiene, 2017,7(2):170-181.
[16]
GB 3095——2012环境空气质量标准[S]. GB 3095——2012 Ambient air quality standards[S].
[17]
张莉,张原,祁士华,等.武汉市洪山区春季PM2.5浓度及多环芳烃组成特征[J]. 中国环境科学, 2015,(8):81-87. Zhang L, Zhang Y, Qi S H, et al. Characteristics of atmospheric PM2.5 and the variation of PAHs in PM2.5 during spring in Hongshan district, Wuhan[J]. China Environmental Science, 2015,(8):81-87.
[18]
宋静,李金泉,王晗,等.甲醛暴露时间延长加剧小鼠哮喘模型肺氧化损伤并促进IL-17表达[J]. 生态毒理学报, 2017,12(1):249-257. Song J, Li J Q, Wang H, et al. Effects of different formaldehyde exposure duration on oxidative stress and IL-17expression in the pulmonary tissue of a mouse asthma model[J]. Asian Journal of Ecotoxicology, 2017,12(1):249-257.
[19]
Nielsen G D, Olsen O, Larsen S T, et al. IgE-mediated sensitisation, rhinitis and asthma from occupational exposures. Smoking as a model for airborne adjuvants?[J]. 2005,216(2):87-105.
[20]
Collins R A, Gualano R C, Zosky G R, et al. Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice[J]. Respiratory Research, 2005, 6(1):142.
[21]
Cui H Y, Huang J W, Lu M M, et al. Antagonistic effect of vitamin E on nAl2O3-induced exacerbation of Th2 and Th17-mediated allergic asthma via oxidative stress[J]. Environmental Pollution, 2019,252:1519-1531.
[22]
Shang S, Li J, Zhao Y, et al. Oxidized graphene-aggravated allergic asthma is antagonized by antioxidant vitamin E in Balb/c mice[J]. Environmental Science and Pollution Research, 2017,24(2):1784-1793.
[23]
Jacquemin B, Siroux V, Sanchez M, et al. Ambient Air pollution and adult asthma incidence in six European cohorts (ESCAPE)[J]. Environmental Health Perspectives, 2015,123(6):613-21.
[24]
Kanchongkittiphon W, Mendell M J, Gaffin J M, et al. Indoor environmental exposures and exacerbation of asthma:An update to the 2000 review by the institute of medicine[J]. Environmental Health Perspectives, 2014,123(1):6-20.
[25]
He M, Ichinose T, Yoshida Y, et al. Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway[J]. Scientific Reports, 2017,7(1):11027.
[26]
Shukla A, Timblin C, Berube K, et al. Inhaled particulate matter causes expression of nuclear factor (NF)-κ B-related genes and oxidantdependent NF-κ B activation in vitro[J]. American Journal of Respiratory Cell and Molecular Biology, 2000,23(2):182-187.
[27]
Mcgwin G, Lienert J, Kennedy J I. Formaldehyde exposure and asthma in children:A systematic review[J]. Ciencia & saude coletiva, 2011, 16(9):3845-3852.
[28]
Wu Y, You H, Ma P, et al. Role of Transient receptor potential ion channels and evoked levels of neuropeptides in a formaldehydeinduced model of asthma in balb/c mice[J]. PLOS ONE, 2013,8(5):e62827.
[29]
Elias J A, Lee C G, Zheng T, et al. New insights into the pathogenesis of asthma[J]. Journal of Clinical Investigation, 2003,111(3):291-7.
[30]
Lloyd C M, Hawrylowicz C M. Regulatory T cells in asthma[J]. Immunity, 2009,31(3):438-449.
[31]
王雪艳.PM2.5对哮喘大鼠气道炎症的影响及机制研究[D]. 天津:天津医科大学, 2015. Wang X Y. Effect and mechanism of PM2.5 on airway inflammation in asthmatic rats[D]. Tianjin:Tianjin Medical University, 2015.
[32]
Kim E K, Choi E J. Compromised MAPK signaling in human diseases:an update[J]. Archives of Toxicology, 2015,89(6):867-882.
[33]
李丹丹,任卫英,朱蕾.p38丝裂原活化蛋白激酶在肺部疾病中的研究进展[J]. 复旦学报(医学版), 2018,258(3):133-137. Li D D, Ren W Y, Zhu L. Progress in research of p38 mitogenactivated protein kinase in pulmonary diseases[J]. Fudan Journal (Medical Edition), 2018,258(3):133-137.
[34]
路雨,李瑶,胡赢丹,等.邻苯二甲酸二异癸酯对小鼠学习记忆的影响[J]. 中国环境科学, 2018,38(1):361-368. Lu Y, Li Y, Hu Y D, et al. Effects of diisononyl phthalate on learning and memory in mice[J]. China Environmental Science, 2018,38(1):361-368.
[35]
Wang J, Huang J, Wang L, et al. Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway[J]. J Thorac Dis, 2017,9(11):4398-4412.
[36]
Lim S K, Moon K C J, Kim G Y, et al. Formaldehyde induces apoptosis through decreased Prx 2via p38MAPK in lung epithelial cells[J]. Toxicology, 2010,271(3):100-106.
[37]
潘秀和,刘超波,孙俊,等.核因子κB信号通路在炎症性肺部疾病中的作用[J]. 中国药理学与毒理学杂志, 2016,30(7):762-769. Pan X H, Liu C B, Sun J, et al. Role of nuclear factor kappa B signaling pathway in inflammatory lung diseases[J]. Chinese Journal of Pharmacology and Toxicology, 2016,30(7):762-769.
[38]
Wei H, Tan K, Sun R, et al. Aberrant Production of Th1/Th2/Th17-Related Cytokines in Serum of C57BL/6Mice after Short-Term Formaldehyde Exposure[J]. International Journal of Environmental Research & Public Health, 2014,11(10):10036-10050.
[39]
Bisset L R, Schmidgrendelmeier P. Chemokines and their receptors in the pathogenesis of allergic asthma:progress and perspective[J]. Current Opinion in Pulmonary Medicine, 2005,11(1):35.
[40]
Ishizuka T, Okajima F, Ishiwara M, et al. Sensitized Mast Cells Migrate Toward the Agen:A Response Regulated by p38MitogenActivated Protein Kinase and Rho-Associated Coiled-Coil-Forming Protein Kinase[J]. The Journal of Immunology, 2001,167(4):2298-2304.
