糖皮质激素受体在慢性气道炎症性疾病激素抵抗中的研究进展
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1.山西医科大学第二临床医学院;2.山西医科大学第二医院 耳鼻咽喉头颈外科 山西省气道炎性疾病神经免疫研究省级重点培育实验室

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国家自然科学基金面上项目(81970865);山西省面上自然基金项目 (201901D111387);山西省回国留学人员科研资助项目(2021-172)。


Research progress of glucocorticoid receptors in corticosteroid resistance in chronic airway inflammatory diseases
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1.Second Clinical Medical College,Shanxi Medical University;2.Department of Otorhinolaryngology Head and Neck Surgery,Shanxi Provincial Key Cultivation Laboratory of Airway Inflammatory Disease neuroimmune Research,the Second Hospital of Shanxi Medical University

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    摘要:

    糖皮质激素具有显著的抗炎作用,广泛应用于慢性气道炎症性疾病(包括变应性鼻炎、慢性鼻-鼻窦炎、哮喘及慢性阻塞性肺疾病等)的治疗。糖皮质激素可与核内糖皮质激素受体(GR)结合并穿过核孔,在细胞核内调控相关基因的表达从而发挥生理学作用。但部分长期使用激素的患者疗效很差甚至无效,即出现糖皮质激素抵抗(CR)现象。CR影响糖皮质激素的治疗效果,导致炎症状态持续,因此了解CR的发生机制对于指导该类疾病的治疗而言至关重要。不同类型的慢性气道炎症性疾病存在的CR机制在一定程度上具有相似性。近年来相关研究提示,CR的发生与激素受体的改变(如表达量、亲和力、基因多态性等)密切相关。为此,本文简要回顾糖皮质激素的治疗机理,对与受体相关的CR发生机制的研究进展进行综述。

    Abstract:

    Glucocorticoids have significant anti-inflammatory effects and are widely used in the treatment of chronic airway inflammatory diseases (including allergic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease, etc.). Glucocorticoids can bind to the glucocorticoid receptors (GR) in the nucleus, pass through the nuclear pores, and then exert physiological effects by regulating the expression of related genes in the nucleus. However, some patients with long-term use of glucocorticoids have poor efficacy or even ineffectiveness, that is, corticosteroid resistance (CR) phenomenon. CR affects the therapeutic effect of glucocorticoids, leading to the persistence of inflammatory state. Therefore, understanding the mechanism of CR is crucial for guiding the treatment of such diseases. The mechanisms of CR in different types of chronic airway inflammatory diseases are similar to some extent. In recent years, studies have suggested that the occurrence of CR is closely related to the changes of GR (such as gene expression, affinity, gene polymorphism, etc.). In this article, we briefly review the therapeutic mechanism of glucocorticoids and summarize the research progress of receptor-related CR mechanism.

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  • 收稿日期:2022-05-31
  • 最后修改日期:2022-07-18
  • 录用日期:2022-07-25
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