|
|
臭氧暴露生物标志物研究探讨
|
Abstract:
臭氧(O3)暴露可引起呼吸、心血管循环等组织或器官的损伤，且伴随O3暴露浓度升高、时间延长，细胞凋亡率升高，组织毒性不断增强。然而目前O3致生物损伤的潜在分子机制还未能被充分认识。生物分子标志物以其高灵敏性、特异性和预警性等特点，已成为在分子毒理学、预防医学、环境医学中研究的重要工具。本文通过综述探讨O3生物毒性评价的生物标志物的主要类型，及其在机体中的作用机制及其应用现状。O3暴露致机体损伤的分子标志物可分为三类：1) 炎症反应生物标志物，包括炎症细胞(如巨噬细胞、白细胞)和炎症因子(如IL-1β、IFN-γ、TNF-α)。2) 氧化应激生物标志物，包括脂质过氧化生物标志物(如MDA、4HNE、iNOS)、抗氧化防御系统生物标志物(如GSH、HSP、Nrf2)。3) 细胞信号通路因子(如Nrf2、NF-κB、TLR、MAPK)。生物标志物的连续监测可预防O3致生物损伤的进一步发展，并为O3致生物损伤机制提供新的研究思路。
Ozone (O3) exposure can cause damage to tissues or organs such as respiration and cardiovascular circulation, and with the increase of O3 exposure concentration and time, the apoptosis rate increases, and the tissue toxicity continues to increase. However, the underlying molecular mechanism of O3-induced biological damage has not been fully understood. Biomarkers have become an important tool in molecular toxicology, preventive medicine and environmental medicine because of their high sensitivity, specificity and early warning. This paper discusses the main types of biomarkers for O3 biotoxicity evaluation, their mechanism of action in the body and their application status through a review. The molecular markers of body damage caused by O3 exposure can be divided into three categories: 1) Inflammatory biomarkers, including inflammatory cells (e.g., macrophages, leukocytes) and inflammatory factors (e.g., IL-1β, IFN-γ, TNF-α). 2) Oxidative stress biomarkers, including lipid peroxidation biomarkers (such as MDA, 4HNE, iNOS), and antioxidant defense system biomarkers (such as GSH, HSP, Nrf2). 3) Cell signaling pathway factors (such as Nrf2, NF-κB, TLR, MAPK). Continuous monitoring of biomarkers can prevent the further development of O3-induced biological damage and provide new research ideas for the mechanism of O3-induced biological damage.
| [1] | 生态环境部. 中国空气质量改善报告(2013-2018年) [R]. 北京: 生态环境部, 2019: 1-5. |
| [2] | Qu, Y.W., Wang, T.J., Cai, Y.F., Wang, S.K., Chen, P.L., et al. (2018) Influence of Atmospheric Particulate Matter on Ozone in Nanjing, China: Observational Study and Mechanistic Analysis. Advances in Atmospheric Sciences, 35, 1381-1395. https://doi.org/10.1007/s00376-018-8027-4 |
| [3] | Li, K., Jacob, D.J., Liao, H., Shen, L., Zhang, Q. and Bates, K.H. (2018) Anthropogenic Drivers of 2013-2017 Trends in Summer Surface Ozone in China. Proceedings of the National Academy of Sciences of the United States of America, 116, 422-427. https://doi.org/10.1073/pnas.1812168116 |
| [4] | Alexis, N.E., Lay, J.C., Hazucha, M., Hazucha, M., Harris, B., Hernandez, M.L., et al. (2010) Low-Level Ozone Exposure Induces Airways Inflammation and Modifies Cell Surface Phenotypes in Healthy Humans. Inhalation Toxicology, 22, 593-600. https://doi.org/10.3109/08958371003596587 |
| [5] | 陈庆梓, 扶招弟, 周玉波, 周丽芬, 杨春涛, 李建华. N-乙酰半胱氨酸减轻O3所致的小鼠肺部炎症反应[J]. 生理学报, 2016, 68(6): 767-774. |
| [6] | Servais, S., Boussouar, A., Molnar, A., Douki, T., Pequignot, J.M. and Favier, R. (2005) Age-Related Sensitivity to Lung Oxidative Stress during Ozone Exposure. Free Radical Research, 39, 305-316.
https://doi.org/10.1080/10715760400011098 |
| [7] | Wagner, J.G., Harkema, J.R., Jiang, Q., Illek, B., Ames, B.N. and Peden, D.B. (2009) γ-Tocopherol Attenuates Ozone-induced Exacerbation of Allergic Rhinosinusitis in Rats. Toxicologic Pathology, 37, 481-491.
https://doi.org/10.1177/0192623309335630 |
| [8] | 梁婷婷, 牛静萍, 张书余, 周骥. 高温热浪与O3交互作用对高血压大鼠影响的实验研究[J]. 科学技术与工程.2018, 18(24): 44-51. |
| [9] | Backus, G.S., Howden, R., Fostel, J., Bauer, A.K., Cho, H.Y., Marzec, J., et al. (2010) Protective Role of Interleukin -10 in Ozone Induced Pulmonary Inflammation. Environmental Health Perspectives, 118, 1721-1727.
https://doi.org/10.1289/ehp.1002182 |
| [10] | Hu, X.Y., He, L.C., Zhang, J.F., Qiu, X.H., Zhang, Y.P., Mo, J.H., et al. (2020) Inflammatory and Oxidative Stress Responses of Healthy Adults to Change in Personal Air Pollutant Exposure. Environmental Pollution, 263, Article ID: 114503. https://doi.org/10.1016/j.envpol.2020.114503 |
| [11] | Li, C.F., Zhang, H., Wei, L.Y., Liu, Q., Xie, M.Q., Weng, J.L., et al. (2022) Role of TRPA1/TRPV1 in Acute Ozone Exposure Induced Murine Model of Airway Inflammation and Bronchial Hyperresponsiveness. Journal of Thoracic Disease, 14, 2698-2711. https://doi.org/10.21037/jtd-22-315 |
| [12] | Perepu, R.S.P., Garcia, C., Dostal, D. and Sethi, R. (2010) Enhanced Death Signaling in Ozone-Exposed Ischemic-Reperfused Hearts. Molecular and Cellular Biochemistry, 336, 55-64. https://doi.org/10.1007/s11010-009-0265-4 |
| [13] | Aquilano, K., Baldelli, S. and Ciriolo, M.R. (2014) Glutathione: New Roles in Redox Signaling for an Old Antioxidant. Frontiers in Pharmacology, 5, Article No. 196. https://doi.org/10.3389/fphar.2014.00196 |
| [14] | Pecorelli, A., McDaniel, D.H., Wortzman, M. and Nelson, D.B. (2020) Protective Effects of a Comprehensive Topical Antioxidant against Ozone-Induced Damage in a Reconstructed Human Skin Model. Archives of Dermatological Research, 313, 139-146. https://doi.org/10.1007/s00403-020-02083-0 |
| [15] | Connor, A.J., Laskin, J.D. and Laskin, D.L. (2012) Ozone-Induced Lung Injury and Sterile Inflammation. Role of Toll-Like Receptor 4. Experimental and Molecular Pathology, 92, 229-235.
https://doi.org/10.1016/j.yexmp.2012.01.004 |
| [16] | 王科霖, 管东波, 宋宏. 呼吸上皮细胞在臭氧气液界面暴露后的氧化损伤效应研究[J]. 环境与健康杂志, 2011, 28(5): 397-400+471. |
| [17] | Rivas-Arancibia, S., Zimbron, L.F.H., Rodriguez-Martinez, E., Maldonado, P.D., Perez, G.B. and Sepulveda-Parada, M. (2015) Oxidative Stress-Dependent Changes in Immune Responses and Cell Death in the Substantia Nigra after Ozone Exposure in Rat. Frontiers in Aging Neuroscience, 7, Article No. 65. https://doi.org/10.3389/fnagi.2015.00065 |
| [18] | Church, A.C., Martin, D.H., Wadsworth, R., Bryson, G., Fisher, A.J., Welsh, D.J. and Peacock, A.J. (2015) The Reversal of Pulmonary Vascular Remodeling through Inhibition of p38 MAPK-Alpha: A Potential Novel Anti-Inflammatory Strategy in Pulmonary Hypertension. American Journal of Physiology—Lung Cellular and Molecular Physiology, 309, L333-L347. https://doi.org/10.1152/ajplung.00038.2015 |
| [19] | Li, F., Zhang, M., Hussain, F., Triantaphyllopoulos, K., Clark, A.R., Bhavsar, P.K., et al. (2011) Inhibition of p38 MAPK-Dependent Bronchial Contraction after Ozone by Corticosteroids. European Respiratory Journal, 3, 933-942.
https://doi.org/10.1183/09031936.00021110 |
| [20] | Longhin, E., Holme, J.A., Gutzkow, K.B., Arlt, V.M., Kucab, J.E., Camatini, M. and Gualtieri, M. (2013) Cell Cycle Alterations Induced by Urban PM2.5 in Bronchial Epithelial Cells: Characterization of the Process and Possible Mechanisms Involved. Particle and Fibre Toxicology, 10, Article No. 63. https://doi.org/10.1186/1743-8977-10-63 |
