山东大学耳鼻喉眼学报 ›› 2026, Vol. 40 ›› Issue (6): 70-75.
• 气道变态反应性疾病:从机制到实践 • 上一篇
苏依琳1,薛金梅1,2
SU Yilin1, XUE Jinmei1,2
摘要: 气道Th2型炎症发病率渐长、临床疗效差。端粒功能障碍与气道Th2型炎症性疾病之间存在着一定的关联。目前国内外研究成果表明,端粒功能障碍可以通过驱动线粒体功能障碍、诱导氧化还原失调促使产生活性氧(reactive oxygen species, ROS),进而引起炎症介质级联反应,最终导致Th2型炎症。本文综述了该主题的研究发现,进一步探讨可能的机制,希望以此开发新的干预措施,为相关疾病的研究及治疗提供新思路和新进展。
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| [1] Busse W W, Kraft M, Rabe K F, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation[J]. Eur Respir J, 2021, 58(2): 2003393. DOI: 10.1183/13993003.03393-2020 [2] Kim B, Rothenberg M E, Sun X, et al. Neuroimmune interplay during type 2 inflammation: symptoms, mechanisms, and therapeutic targets in atopic diseases[J]. J Allergy Clin Immunol, 2024, 153(4): 879-893. DOI: 10.1016/j.jaci.2023.08.017 [3] Giombi F, Pace G M, Pirola F, et al. Airways type-2 related disorders: multiorgan, systemic or syndemic disease?[J]. Int J Mol Sci, 2024, 25(2): 730. DOI: 10.3390/ijms25020730 [4] Gavia-García G, Rosado-Pérez J, Arista-Ugalde T L, et al. Telomere length and oxidative stress and its relation with metabolic syndrome components in the aging[J]. Biology(Basel), 2021, 10(4): 253. DOI: 10.3390/biology10040253 [5] Jones-Weinert C, Mainz L, Karlseder J. Telomere function and regulation from mouse models to human ageing and disease[J]. Nat Rev Mol Cell Biol, 2025, 26(4): 297-313. DOI: 10.1038/s41580-024-00800-5 [6] 赵兵, 周斌. 人胃黏膜端粒功能障碍与慢性萎缩性胃炎的相关性研究[J]. 中华消化杂志, 2023, 43(1): 4751. DOI: 10.3760/cma.j.cn311367-20220921-00468 [7] Glorieux C, Liu S H, Trachootham D, et al. Targeting ROS in cancer: rationale and strategies[J]. Nat Rev Drug Discov, 2024, 23(8): 583-606. DOI: 10.1038/s41573-024-00979-4 [8] Shim H S, Iaconelli J, Shang X Y, et al. TERT activation targets DNA methylation and multiple aging hallmarks[J]. Cell, 2024, 187(15): 4030-4042.e13. DOI: 10.1016/j.cell.2024.05.048 [9] Piñeiro-Hermida S, Martínez P, Blasco M A. Short and dysfunctional telomeres protect from allergen-induced airway inflammation[J]. Aging Cell, 2021, 20(5): e13352. DOI: 10.1111/acel.13352 [10] Smith E M, Pendlebury D F, Nandakumar J. Structural biology of telomeres and telomerase[J]. Cell Mol Life Sci, 2020, 77(1): 61-79. DOI: 10.1007/s00018-019-03369-x [11] Mir S M, Samavarchi Tehrani S, Goodarzi G, et al. Shelterin complex at telomeres: implications in ageing[J]. Clin Interv Aging, 2020, 15: 827-839. DOI: 10.2147/CIA.S256425 [12] Heba A C, Toupance S, Arnone D, et al. Telomeres: New players in immune-mediated inflammatory diseases?[J]. J Autoimmun, 2021, 123: 102699. DOI: 10.1016/j.jaut.2021.102699 [13] Lin J, Epel E. Stress and telomere shortening: insights from cellular mechanisms[J]. Ageing Res Rev, 2022, 73: 101507. DOI: 10.1016/j.arr.2021.101507 [14] Lex K, Maia Gil M, Lopes-Bastos B, et al. Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish[J]. Proc Natl Acad Sci USA, 2020, 117(26): 15066-15074. DOI: 10.1073/pnas.1920049117 [15] Xue J M, Liu Z Z, Liao Y, et al. Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis[J]. iScience, 2023, 27(1): 108615. DOI: 10.1016/j.isci.2023.108615 [16] Sies H, Jones D P. Reactive oxygen species(ROS)as pleiotropic physiological signalling agents[J]. Nat Rev Mol Cell Biol, 2020, 21(7): 363-383. DOI: 10.1038/s41580-020-0230-3 [17] 周颖东, 张梦娴, 王青玲, 等. 氧化应激在老年性聋发病机制中的研究进展[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 72-78,91. DOI: 10.6040/j.issn.1673-3770.0.2022.518 [18] Zhang J, Wei Y H, Yue Y B, et al. RIPK4 promotes oxidative stress and ferroptotic death through the downregulation of ACSM1[J]. Proc Natl Acad Sci USA, 2024, 121(40): e2410628121. DOI: 10.1073/pnas.2410628121 [19] 中华医学会变态反应学分会. 2型炎症性疾病机制及靶向治疗专家共识[J]. 中华医学杂志, 2022, 102(42): 3349-3373. DOI: 10.3760/cma.j.cn112137-20220628-01431 [20] Zang Y, Liu S R, Rao Z B, et al. Retinoid X receptor gamma dictates the activation threshold of group 2 innate lymphoid cells and limits type 2 inflammation in the small intestine[J]. Immunity, 2023, 56(11): 2542-2554. DOI: 10.1016/j.immuni.2023.08.019 [21] Vlaykov A N, Tacheva T T, Vlaykova T I, et al. Serum and local IL-4, IL-5, IL-13 and immunoglobulin E in allergic rhinitis[J]. Postepy Dermatol Alergol, 2020, 37(5): 719-724. DOI: 10.5114/ada.2020.100483 [22] Chakravarti D, Hu B L, Mao X Z, et al. Telomere dysfunction activates YAP1 to drive tissue inflammation[J]. Nat Commun, 2020, 11(1): 4766. DOI: 10.1038/s41467-020-18420-w [23] Lanna A, Vaz B, D'Ambra C, et al. An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory[J]. Nat Cell Biol, 2022, 24(10): 1461-1474. DOI: 10.1038/s41556-022-00991-z [24] Chakravarti D, LaBella K A, DePinho R A. Telomeres: history, health, and hallmarks of aging[J]. Cell, 2021, 184(2): 306-322. DOI: 10.1016/j.cell.2020.12.028 [25] Dong H, Xia Y Y, Jin S L, et al. Nrf2 attenuates ferroptosis-mediated IIR-ALI by modulating TERT and SLC7A11[J]. Cell Death Dis, 2021, 12(11): 1027. DOI: 10.1038/s41419-021-04307-1 [26] Gao X Y, Yu X, Zhang C, et al. Telomeres and mitochondrial metabolism: implications for cellular senescence and age-related diseases[J]. Stem Cell Rev Rep, 2022, 18(7): 2315-2327. DOI: 10.1007/s12015-022-10370-8 [27] Miwa S, Kashyap S, Chini E, et al. Mitochondrial dysfunction in cell senescence and aging[J]. J Clin Invest, 2022, 132(13): e158447. DOI: 10.1172/JCI158447 [28] Chen Z, Han F F, Du Y, et al. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions[J]. Signal Transduct Target Ther, 2023, 8(1): 70. DOI: 10.1038/s41392-023-01332-8 [29] Lee J H, Paull T T. Cellular functions of the protein kinase ATM and their relevance to human disease[J]. Nat Rev Mol Cell Biol, 2021, 22(12): 796-814. DOI: 10.1038/s41580-021-00394-2 [30] Batsios G, Taglang C, Gillespie A M, et al. Imaging telomerase reverse transcriptase expression in oligodendrogliomas using hyperpolarized δ-[1-13C] -gluconolactone[J]. Neurooncol Adv, 2023, 5(1): vdad092. DOI: 10.1093/noajnl/vdad092 [31] Wiley C D, Campisi J. The metabolic roots of senescence: mechanisms and opportunities for intervention[J]. Nat Metab, 2021, 3(10): 1290-1301. DOI: 10.1038/s42255-021-00483-8 [32] Reis J, Gorgulla C, Massari M, et al. Targeting ROS production through inhibition of NADPH oxidases[J]. Nat Chem Biol, 2023, 19(12): 1540-1550. DOI: 10.1038/s41589-023-01457-5 [33] Niu B Y, Liao K X, Zhou Y X, et al. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy[J]. Biomaterials, 2021, 277: 121110. DOI: 10.1016/j.biomaterials.2021.121110 [34] Maniaci A, Via L L, Lechien J R, et al. Hearing loss and oxidative stress: a comprehensive review[J]. Antioxidants(Basel), 2024, 13(7): 842. DOI: 10.3390/antiox13070842 [35] Li J, Xu P L, Chen S S. Research progress on mitochondria regulating tumor immunity[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2024, 53(1): 1-14. DOI: 10.3724/zdxbyxb-2023-0484 [36] Wang Y, Yuan H L, Shen D, et al. Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway[J]. Biomed Pharmacother, 2024, 177: 116894. DOI: 10.1016/j.biopha.2024.116894 [37] 刘玉卓, 吕威, 王威清. 单细胞转录组测序技术在呼吸道2型炎性疾病中的研究进展[J]. 中华耳鼻咽喉头颈外科杂志, 2023, 58(12): 1266-1271. DOI: 10.3760/cma.j.cn115330-20230413-00169 [38] 韩晋博, 王威清, 朱真真, 等. 慢性鼻窦炎的鼻腔黏膜上皮细胞研究进展[J].中华耳鼻咽喉头颈外科杂志, 2022, 57(1): 78-81. DOI: 10.3760/cma.j.cn115330-20210303-00103 [39] Rehman R, Jaiswal A, Agrawal A, et al. Ku70 modulation alleviates murine allergic asthma features and restores mitochondrial function in lungs[J]. Mitochondrion, 2021, 57: 76-87. DOI: 10.1016/j.mito.2020.12.005 [40] Chang-Chien J, Kuo M L, Tseng Y L, et al. Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies[J]. Ecotoxicol Environ Saf, 2024, 281: 116650. DOI: 10.1016/j.ecoenv.2024.116650 [41] Guo Q, Jin Y Z, Chen X Y, et al. NF-κB in biology and targeted therapy: new insights and translational implications[J]. Signal Transduct Target Ther, 2024, 9(1): 53. DOI: 10.1038/s41392-024-01757-9 [42] Karadogan B, Beyaz S, Gelincik A, et al. Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control[J]. J Asthma, 2022, 59(4): 663-672. DOI: 10.1080/02770903.2020.1870129 [43] Nagasaki T, Schuyler A J, Zhao J M, et al. 15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation[J]. J Clin Invest, 2022, 132(1): e151685. DOI: 10.1172/JCI151685 [44] Wang X F, Xu W J, Wang F F, et al. Telomere length and development of systemic lupus erythematosus: a mendelian randomization study[J]. Arthritis Rheumatol, 2022, 74(12): 1984-1990. DOI: 10.1002/art.42304 |
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