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

Research progress of glucocorticoid receptors in corticosteroid resistance of chronic airway inflammatory diseases

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GR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，并对与受体相关的CR发生机制的研究进展进行综述。

关键词:变应性鼻炎;慢性气道炎症性疾病;糖皮质激素;激素抵抗;糖皮质激素受体

Abstract:

Glucocorticoids have significant anti-inflammatory effects, which are widely used to treat chronic airway inflammatory diseases, including allergic rhinitis, chronic rhinosinusitis, asthma and chronic obstructive pulmonary disease. Glucocorticoids can bind to intranuclear glucocorticoid receptors (GR), 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, the corticosteroid resistance (CR) phenomenon. CR affects the therapeutic effect of glucocorticoids, which will lead to the persistence of an inflammatory state. Therefore, understanding the mechanism of CR is crucial for guiding the treatment of the diseases. The mechanisms of CR are similar to some extent in different types of chronic airway inflammatory diseases. Recent studies suggest that the occurrence of CR is closely related to the changes (such as gene expression, affinity, gene polymorphism, etc.) in GR. In this paper, the therapeutic mechanism of glucocorticoids was briefly reviewed, and the research progress on the mechanism of CR related to receptors was reviewed.

Key words:Allergic rhinitis;Chronic airway inflammatory diseases;Glucocorticoids;Corticosteroid resistance;Glucocorticoid receptors