褪黑素在哮喘发病和病程中的作用机制研究进展

doi:10.3969/j.issn.1674-8115.2022.05.016

摘要/Abstract

摘要：

褪黑素（melatonin）是由松果体分泌的激素之一，其调控昼夜节律和改善睡眠的功效已被广泛研究和证实。已有研究认为褪黑素过量或分泌紊乱能导致不良的健康效应。近年来，不断积累的证据显示褪黑素在抗炎、抗癌、免疫调节等方面发挥重要作用。加之褪黑素不仅可以在人体合成，且易于通过外源性途径获取，因此，其对人体健康的影响备受关注。该文以褪黑素参与气道炎症和气道重塑调控为切入点，系统检索、筛选了截至2022年2月的相关文献37篇，分析了褪黑素对哮喘的影响及相关机制。结果显示，褪黑素一方面可以通过抑制磷酸化信号通路影响基因转录、翻译，阻断核因子κB（nuclear factor-κB，NF-κB）的激活，进而改变呼吸道细胞因子和炎症细胞的表达，减少嗜酸性粒细胞等炎症细胞的生成和募集，抑制白细胞介素-1β（interleukin-1β，IL-1β）、IL-4、IL-6、胱天蛋白酶-1（caspase-1）等细胞因子和酶，减少黏液的产生，发挥抑制气道炎症的作用，并可以拮抗哮喘的外源性加重和特应性进程。另一方面，褪黑素能够通过作用于基质金属蛋白酶9（matrix metalloproteinase-9，MMP-9），减少胶原沉积，抑制杯状细胞增生，改善平滑肌细胞表型而实现抑制气道重塑。上述结论均提示褪黑素具有通过气道炎症和气道重塑调控哮喘发病进程的潜力，围绕褪黑素的免疫调节功能开展深入探索有望为哮喘防治提供新思路。

关键词: 褪黑素, 哮喘, 气道炎症, 气道重塑

Abstract:

Melatonin is one of the hormones secreted by the pineal gland. The efficacy of melatonin in regulating circadian rhythm and improving sleep has been widely explored and confirmed. Studies have shown that excessive secretion or disordered melatonin can lead to adverse health effects. In recent years, accumulated evidence shows that melatonin plays an important role in anti-inflammatory, anti-cancer, immune regulation, and so on. In addition, melatonin can not only be synthesized in the human body, but also be easily obtained through external sources. Therefore, its impact on human body has attracted much attention. Based on the involvement of melatonin in airway inflammation and airway remodeling, this study systematically searched and screened 37 relevant literatures up to February 2022 and analyzed the effect of melatonin on asthma and its related mechanisms. The results showed that, on one hand, melatonin could affect gene transcription and translation by inhibiting phosphorylation signaling pathway and blocking the activation of nuclear factor-κB (NF-κB), thereby changing the expression of respiratory cytokines and inflammatory cells, reducing the generation and recruitment of eosinophils and other inflammatory cells, inhibiting cytokines and enzymes such as interleukin-1β (IL-1β), IL-4, IL-6 and caspase-1, reducing the production of mucus, playing a role in inhibiting airway inflammation, and also antagonizing the exogenous exacerbation and atopic process of asthma. On the other hand, melatonin can inhibit airway remodeling by acting on matrix metalloproteinase-9 (MMP-9), reducing collagen deposition, inhibiting goblet cell proliferation and improving smooth muscle cell phenotype. All these findings suggest that melatonin has the potential to regulate the pathogenesis of asthma by inhibiting airway inflammation and remodeling. Further exploration on the immunomodulatory function of melatonin is expected to provide new ideas for the prevention and treatment of asthma.

Key words: melatonin, asthma, airway inflammation, airway remodeling

中图分类号:

R562.2+5

康文慧, 陈仪婷, 赵安达, 李荣, 李生慧. 褪黑素在哮喘发病和病程中的作用机制研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(5): 667-672.

KANG Wenhui, CHEN Yiting, ZHAO Anda, LI Rong, LI Shenghui. Research progress of the mechanism of melatonin in the pathogenesis and course of asthma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(5): 667-672.

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