金黄色葡萄球菌调节mucin表达影响鼻黏膜黏液屏障在慢性鼻窦炎发病中的作用及其机制研究

慢性鼻窦炎是鼻科高发病之一，严重影响患者生活质量。在慢性鼻窦炎病程中，鼻黏膜局部菌群失调及金黄色葡萄球菌等细菌的毒力改变影响疾病进展及预后。金黄色葡萄球菌可在鼻黏膜局部形成细菌生物膜、释放多种毒力因子或直接进入上皮细胞形成胞内金黄色葡萄球菌，持续作用于鼻黏膜，影响黏膜细胞多种黏蛋白(mucin)基因表达。结合前期结果，我们认为金黄色葡萄球菌影响黏蛋白mucin表达可改变鼻黏膜局部黏液层微环境，影响慢性鼻窦炎的发病。本课题依据前期发现的差异表达mucin基因为核心，通过构建金黄色葡萄球菌与鼻黏膜上皮细胞共培养模型及慢性鼻窦炎小鼠模型，检测并干预相关基因，对金黄色葡萄球菌调节mucin表达，继而影响上皮细胞纤毛运动、紧密连接、局部炎症反应等慢性鼻窦炎病理改变进行研究。以明确金黄色葡萄球菌调节mucin表达在慢性鼻窦炎黏膜损伤中的作用及机制，为进一步阐明慢性鼻窦炎病理机制提供实验及理论证据。

Chronic rhinosinusitis (CRS) is one of the common diseases in the department of rhinology, which seriously affects the quality of life of patients. In the course of CRS, local dysbacteriosis of the nasal mucosa and virulence changes of Staphylococcus aureus (S. aureus) and other bacteria affect the progress and prognosis of the disease. S. aureus can form bacterial biofilm locally in the nasal mucosa and release a variety of virulence factors, or directly enter the epithelial cells to form intracellular S. aureus, which continuously acts on the nasal mucosa and affects the expression of various mucin gene expression. Combined with the previous results, we believe that S. aureus can affect mucin expression, change the local mucosa microenvironment in the nasal mucosa, and affect the incidence of CRS. This project is based on the previous result of differential expressed mucin genes as the target genes. We will establish S. aureus and human epithelial cells co-culture model and CRS mouse model, detect and interfere related genes, to study the process that S. aureus regulate mucin expression, which affects the epithelial ciliary movement, tight junction and inflammatory reaction of the pathological changes in CRS. To clarify the role and mechanism of S. aureus in regulating mucin expression in the mucosal injury of CRS, and to provide the experimental and theoretical evidence for further elucidation of the pathological mechanism of CRS.