氧化应激在儿童病毒性肺炎中的作用机制及中西医干预研究进展

Mechanism of oxidative stress in children with viral pneumonia and research advances in integrated Chinese and western medicine interventions

摘要

儿童病毒性肺炎是常见的下呼吸道感染性疾病，氧化应激在其发生发展中起着关键作用。病毒感染可诱发活性氧自由基风暴，打破机体氧化-抗氧化平衡，并通过激活Toll样受体、核因子κB及核转录因子红系2相关因子2等关键信号通路，促进病毒复制、过度炎症反应与肺组织损伤。目前，针对该病的抗氧化治疗研究已成为热点。本文在阐明氧化应激核心机制的基础上，进一步综述了中西医的干预策略。深入探讨氧化应激机制并整合中西医抗氧化策略，将为儿童病毒性肺炎的临床防治提供新的思路与药物研发靶点。

Abstract

Viral pneumonia is a common lower respiratory tract infection in children, and oxidative stress plays a pivotal role in its occurrence and development. Viral infection can induce a storm of reactive oxygen species, disrupting the systemic oxidant-antioxidant balance, and promoting viral replication, excessive inflammatory responses and lung tissue damage by activating key signaling pathways such as Toll-like receptors (TLR), nuclear factor kappa-B (NF-κB), and nuclear factor erythroid-2 related factor 2 (Nrf2). Currently, antioxidant therapy for this disease has become a focus of research. Based on elucidating the core mechanism of oxidative stress, this article reviews interventional strategies of traditional Chinese and western medicine. An in-depth exploration of the oxidative stress mechanism is made and antioxidant strategies based on TCM and western medicine are integrated, which will provide novel insights and drug development targets for the clinical prevention and treatment of viral pneumonia in children.

关键词

病毒性肺炎 / 氧化应激 / 信号通路 / 抗氧化剂 / 中医药治疗 / 儿童

Key words

Viral pneumonia / Oxidative stress / Signaling pathway / Antioxidant / Traditional Chinese medicine therapy / Child

参考文献

[1] 占达丽, 李敏, 王文慧, 等 . 2017—2020年海南省4 132例儿童肺炎病例病原菌检测结果分析[J]. 华南预防医学, 2022, 48(5): 627-629.

[2] 麦文慧, 卓珠琳, 郑青, 等 . 海口市儿童急性下呼吸道细菌感染的病原学特征及耐药性分析[J]. 中国热带医学, 2021, 21(9): 833-838.

[3] Pratt MTG, Abdalla T, Richmond PC, et al. Prevalence of respiratory viruses in community—acquired pneumonia in children: a systematic review and meta—analysis[J]. Lancet Child Adolesc Health, 2022, 6(8): 555-570.

[4] Cristerna TGH, González Saldaa N, Hernández PM, et al. Leukocytes and C—reactive protein levels in children with influenza—positive and influenza—negative viral pneumonia in a third—level pediatric center in Mexico city from 2011 to 2016[J]. J Pediatr Infect Dis Soc, 2021, 6(9): e333.

[5] 刘媛, 范中娥, 范方勇, 等 . 桑夏扶正汤剂联合雾化治疗小儿病毒性肺炎的临床效果及安全性评价[J]. 解放军医药杂志, 2020, 32(6): 56-59.

[6] Ren GL, Wang XF, Xu J, et al. Comparison of acute pneumonia caused by SARS—COV—2 and other respiratory viruses in children: a retrospective multi—center cohort study during COVID—19 outbreak[J]. Mil Med Res, 2021, 8(1): 13.

[7] Brenes—Chacon H, Garcia—Mauriño C, Moore—Clingenpeel M, et al. Age—dependent interactions among clinical characteristics, viral loads and disease severity in young children with respiratory syncytial virus infection[J]. Pediatr Infect Dis J, 2021, 40(2): 116-122.

[8] Guo YX, Liu YR, Zhao SH, et al. Oxidative stress—induced FABP5 S—glutathionylation protects against acute lung injury by suppressing inflammation in macrophages[J]. Nat Commun, 2021, 12(1): 7094.

[9] Sharma A, Tewari D, Nabavi SF, et al. Reactive oxygen species modulators in pulmonary medicine[J]. Curr Opin Pharmacol, 2021, 57: 157-164.

[10] 王保华, 李赛美, 左俊岭 . 白虎清解汤对小鼠流感病毒性肺炎氧化应激的动态干预作用[C]//中华中医药学会仲景学说分会. 仲景医学求真(续三). 广州中医药大学第一附属医院, 2009: 399-401.

[11] Xu W, Zhao T, Xiao H . The implication of oxidative stress and AMPK—Nrf2 antioxidative signaling in pneumonia pathogenesis[J]. Front Endocrinol (Lausanne), 2020, 11: 400.

[12] Noonong K, Chatatikun M, Surinkaew S, et al. Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis[J]. Front Immunol, 2023, 14: 1275001.

[13] Hosakote YM, Liu T, Castro SM, et al. Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes[J]. Am J Respir Cell Mol Biol, 2009, 41(3): 348-357.

[14] Wang F, Xie R . Knockdown of THBS1 inhibits inflammatory damage and oxidative stress in in vitro pneumonia model by regulating NF—κB signaling pathway[J]. Allergol Immunopathol (Madr), 2025, 53(3): 17-22.

[15] To T, Terebessy E, Zhu J, et al. Does early life exposure to exogenous sources of reactive oxygen species (ROS) increase the risk of respiratory and allergic diseases in children? A longitudinal cohort study[J]. Environ Health, 2022, 21(1): 90.

[16] Malaviya R, Meshanni JA, Sunil VR, et al. Role of macrophage bioenergetics in N—acetylcysteine—mediated mitigation of lung injury and oxidative stress induced by nitrogen mustard[J]. Toxicol Appl Pharmacol, 2024, 485: 116908.

[17] Ahmad S, Nasser W, Ahmad A . Epigenetic mechanisms of alveolar macrophage activation in chemical—induced acute lung injury[J]. Front Immunol, 2024, 15: 1488913.

[18] Steingruber L, Handtke S, Schweiger F, et al. Histopathological analysis of respiratory muscles in patients with acute COVID—19 infection[J]. Cell Tissue Res, 2025, 401(1): 59-68.

[19] Barber TM, Kabisch S, Pfeiffer AFH, et al. Optimised skeletal muscle mass as a key strategy for obesity management[J]. Metabolites, 2025, 15(2): 85.

[20] 高萍萍, 宋湘 . 氧化应激对心血管疾病影响的研究进展[J]. 心血管康复医学杂志, 2023, 32(2): 163-166.

[21] Gouda NA, Zhakupova A, Abdelaal AM, et al. The interplay involving oxidative stress and autophagy: Mechanisms, implications, and therapeutic opportunities[J]. Exp Mol Pathol, 2025, 143: 104989.

[22] Tepebaşı MY, İlhan İ, Temel EN, et al. Investigation of inflammation, oxidative stress, and DNA damage in COVID—19 patients[J]. Cell Stress Chaperones, 2023, 28(2): 191-199.

[23] Chang JW, Chen HC, Hu HZ, et al. Phthalate exposure and oxidative/nitrosative stress in childhood asthma: a nested case—control study with propensity score matching[J]. Biomedicines, 2022, 10(6): 1438.

[24] Chaudhary P, Janmeda P, Docea AO, et al. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases[J]. Front Chem, 2023, 11: 1158198.

[25] Carrasco—García Á, Herrera G, de Graaff LCG, et al. Role of mitochondrial function in the oxidative stress profile of children with Prader—Willi syndrome[J]. Free Radic Biol Med, 2025, 237: 397-402.

[26] Li M, Li M, Hou Y, et al. Ferroptosis triggers airway inflammation in asthma[J]. Ther Adv Respir Dis, 2023, 17: 17534666231208628.

[27] Andrade AS, Bentes AA, Diniz LM, et al. Association between single—nucleotide polymorphisms in Toll—like receptor 3 (tlr3), tlr7, tlr8 and tirap genes with severe symptoms in children presenting COVID—19 [J]. Viruses, 2024, 17(1): 35.

[28] Kim CU, Lim D, Kim YS, et al. Influenza viral matrix 1 protein aggravates viral pathogenicity by inducing TLR4—mediated reactive oxygen species production and apoptotic cell death[J]. Cell Death Dis, 2023, 14(3): 228.

[29] Gong C, Ma J, Deng Y, et al. S100A9 ^—/— alleviates LPS—induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis [J]. Biomed Pharmacother, 2024, 172: 116233.

[30] He M, Ren Z, Goraya MU, et al. Anti—influenza drug screening and inhibition of apigetrin on influenza A virus replication via TLR4 and autophagy pathways[J]. Int Immunopharmacol, 2023, 124(Pt B): 110943.

[31] Watanabe N, Fujita Y, Nakayama J, et al. Anomalous epithelial variations and ectopic inflammatory response in chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol, 2022, 67(6): 708-719.

[32] Tie Y, Liu H, Zhang T, et al. Natural products alleviate viral pneumonia by modulating inflammatory and oxidative—stress pathways[J]. Front Pharmacol, 2025, 16: 1657829.

[33] Schreck R, Rieber P, Baeuerle PA . Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF—kappa B transcription factor and HIV—1[J]. EMBO J, 1991, 10(8): 2247-2258.

[34] 倪雯婷, 马大龙, 邵骏菁, 等 . 基于网络药理学和实验验证探索荆防合剂治疗甲型H1N1流感的作用机制[J]. 中国实验方剂学杂志, 2022, 28(12): 200-209.

[35] Niri P, Saha A, Polopalli S, et al. β—Caryophyllene attenuates oxidative stress and inflammatory response in LPS induced acute lung injury by targeting ACE2/MasR and Nrf2/HO—1/NF—κB axis[J]. Biochem Biophys Res Commun, 2025, 746: 151286.

[36] Sivandzade F, Prasad S, Bhalerao A, et al. NRF2 and NF—κB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches[J]. Redox Biol, 2019, 21: 101059.

[37] Toscanelli W, Fracella M, De Angelis M, et al. NRF2 antioxidant response and interferon—stimulated genes are differentially expressed in SARS—CoV—2—positive young subjects[J]. Immun Inflamm Dis, 2025, 13(1): e70109.

[38] Jin X, Chen L, Yang Y, et al. Adverse effects of Nrf2 in different organs and the related diseases[J]. Antioxid Redox Signal, 2025, 42(16—18): 973-985.

[39] Shaw P, Chattopadhyay A . Nrf2—ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms[J]. J Cell Physiol, 2020, 235(4): 3119-3130.

[40] Cho HY, Imani F, Miller—DeGraff L, et al. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease[J]. Am J Respir Crit Care Med, 2009, 179(2): 138-150.

[41] Georgiou—Siafis SK, Tsiftsoglou AS . The key role of GSH in keeping the redox balance in mammalian cells: mechanisms and significance of GSH in detoxification via formation of conjugates[J]. Antioxidants (Basel), 2023, 12(11): 1953.

[42] Checconi P, De Angelis M, Marcocci ME, et al. Redox—Modulating agents in the treatment of viral infections[J]. Int J Mol Sci, 2020, 21(11): 4084.

[43] Anwar S, Sarwar T, Khan AA, et al. Therapeutic applications and mechanisms of superoxide dismutase (SOD) in different pathogenesis[J]. Biomolecules, 2025, 15(8): 1130.

[44] Moradi—Marjaneh R, Hassanian SM, Fiuji H, et al. Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer[J]. J Cell Physiol, 2018, 233(8): 5613-5622.

[45] Lin X, Wang R, Zou W, et al. The influenza virus H5N1 infection can induce ROS production for viral replication and host cell death in A549 cells modulated by human Cu/Zn superoxide dismutase (SOD1) overexpression[J]. Viruses, 2016, 8(1): 13.

[46] 郑敏敏, 柳洁, 赵清 . 药用植物黄芩的生物学研究进展及展望[J]. 生物技术通报, 2023, 39(2): 10-23.

[47] 周思瑶, 游雷鸣, 张海丽, 等 . 汉黄芩素对LPS—ATP诱导的巨噬细胞氧化应激的抑制作用[J]. 中国免疫学杂志, 2020, 36(3): 257-260.

[48] Li W, Wang X, Chen Y, et al. Luteolin—7—O—glucoside promotes macrophage release of IFN—β by maintaining mitochondrial function and corrects the disorder of glucose metabolism during RSV infection[J]. Eur J Pharmacol, 2024, 963: 176271.

[49] Liu H, You L, Wu J, et al. Berberine suppresses influenza virus—triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS[J]. J Leukoc Biol, 2020, 108(1): 253-266.

[50] 张来, 张秀英, 魏晨浩, 等 . 定喘颗粒对呼吸道合胞病毒肺炎模型大鼠肺组织氧化应激及Nrf2/Keap1/HO—1/NQO1信号通路的影响[J]. 中医杂志, 2025, 66(15): 1588-1596.