激素抵抗型哮喘发病机制和维生素D对其部分机制的影响

Pathogenesis of steroid-resistant asthma and the influence of vitamin D

摘要:

糖皮质激素（GC）是目前最有效控制持续性哮喘的药物。然而，哮喘人群对GC治疗效果存在明显差异。激素抵抗型（SR）哮喘应用高剂量GC治疗效果不佳，且严重影响该类患者的生活质量，甚至危及生命。因此探究SR哮喘发病的具体机制及针对性治疗策略具有重要意义。近年来发现多种发病机制参与SR哮喘的发生发展，包括糖皮质激素受体（GR）与GC结合力的降低、GRβ表达的增加、核转录因子活化蛋白1（AP-1）和核因子-κB（NF-κB）的过度激活、组蛋白乙酰化的异常及免疫介导的细胞因子失调等。此外，国内外多项研究表明维生素D可提高SR哮喘人群对GC的敏感性。该文就SR哮喘发病机制及维生素D参与其相关机制综述如下。

Abstract:

Glucocorticoid (GC) is currently the most effective drug for controlling persistent asthma; however, there is a significant difference in the response to GC among patients with asthma. Steroid-resistant asthma is one of the subtypes of asthma and has poor response to high-dose GC treatment. It may affect the quality of life of patients and even threaten their lives. Therefore, it is of great significance to explore the pathogenesis of steroid-resistant asthma and related targeted treatment strategy. In recent years, a variety of pathogeneses have been found to participate in the development and progression of steroid-resistant asthma, including the reduction in the binding between GC receptor and GC, the increase in the expression of GC receptor β, over-activation of nuclear transcription factor activating protein 1 and nuclear factor-κB, abnormality in histone acetylation, and immune-mediated cytokine dysregulation. In addition, many studies have shown that vitamin D can improve the sensitivity to GC among patients with steroid-resistant asthma. This article reviews the pathogenesis of steroid-resistant asthma and the influence of vitamin D.