慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）是一类临床常见、具有高度异质性、发病机制复杂的鼻窦黏膜慢性炎性疾病。糖皮质激素作为临床中治疗慢性鼻-鼻窦炎的一线药物，其生物学效应主要由糖皮质激素受体（GR）介导。临床中部分患者尽管规范应用糖皮质激素治疗，仍对其治疗不敏感，出现激素抵抗。激素敏感或抵抗状态下，GR亚型的表达及信号转导是否存在差异尚未阐明。本课题拟通过体内和体外研究，围绕GR多种亚型对CRSwNP的糖皮质激素敏感/抵抗的影响，明确体内和体外糖皮质激素作用下组织和细胞层面GR亚型的表达差异及其与激素敏感/抵抗的相关性；明确GR亚型及相关信号途径和凋亡途径调控糖皮质激素敏感性的机制；同时观察糖皮质激素敏感/抵抗型的组织局部和外周白细胞中GR亚型、炎性标志物和信号分子的相关性，探索外周相关指标反映组织局部指标的可能性。为从GR亚型角度干预CRSwNP糖皮质激素疗效提供理论依据。

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common, highly heterogeneous and complex inflammatory disease of sinus mucosa. Glucocorticoid is the first-line drug for the treatment of CRSwNP. Its biological effects are mainly mediated by glucocorticoid receptor (GR). There are some patients who are not sensitive to glucocorticoid and resistant to glucocorticoid despite the standard application of glucocorticoid therapy. However, the expression and signal transduction of these GR subtypes in different glucocorticoid sensitive states are still unclear. In this study, we intend to study the effects of GR subtypes on glucocorticoid sensitivity/resistance of CRSwNP in vivo and in vitro, to clarify the differences in the expression of GR subtypes at tissue and cell levels under the action of glucocorticoid and their correlation with glucocorticoid sensitivity/resistance, to clarify the regulation of GR subtypes and related signaling pathways and apoptotic pathways on glucocorticoid sensitivity. At the same time, we observed the correlation of GR subtypes, inflammatory markers and signaling molecules between glucocorticoid-sensitive/resistant tissue and peripheral blood white cells, and explored the possibility that the related indicators of peripheral blood white cells could reflect the local indicators of tissue. Then this study may provide a theoretical basis for the intervention of glucocorticoid therapy for CRSwNP from the GR subtypes and related factors.