【作者】 高枫；

【导师】 蔡绍曦；

【作者基本信息】 第一军医大学 ， 呼吸内科学， 2006， 硕士

【摘要】 研究背景 支气管哮喘是常见的慢性疾病，研究哮喘的分子病理机制是有效控制哮喘的前提。针对哮喘的遗传学基础、与环境因素的关系、免疫机制等研究证实哮喘是受遗传和环境因素影响的复杂的多基因疾病。同时也发现很多尚不明了和有争议的问题，其中关于嗜酸性粒细胞(EOS)的作用是最大的争论焦点之一。 EOS是参与哮喘病理过程的炎症细胞之一。目前已经证明哮喘中EOS作用过程如下：抗原递呈细胞将抗原递呈到细胞表面，导致Th2细胞分化并产生Th2细胞因子，其中IL-5、IL-13、GM-CSF促进骨髓CD34~+干细胞向EOS方向分化，在IL-5诱导下，细胞从骨髓向血管迁移；IL-4、IL-13诱导血管细胞粘附分子(VCAM-1)表达，结合到其在EOS表面受体(VLA-4)，使得血管内EOS利于穿过血管壁，到达Th2细胞介导的炎症反应部位；活化的EOS作用于气道壁多种细胞，或者分泌Th2细胞因子，导致气道粘膜以EOS浸润为特征的炎症、粘液分泌增加、气道高反应性、基底膜胶原沉积等哮喘病理生理过程。 而哮喘中EOS在活化、发挥炎症效应过程中细胞内部信号转导调节、分子调控机制以及这些细胞内部分子调控与细胞活化、发挥其在哮喘中病理作用的关系有待进一步探讨。我们实验室从哮喘发作过程中EOS基因差异表达入手，希望发现哮喘发作过程中EOS某些有意义的表达变化的基因，以及这些基因表更多还原

【Abstract】 BackgroundAs a common chronic disease, the incidence of asthma increase year after year. It is fundamental that investigate the molecular mechanism of asthma which including genetic factors, environment, immunity, the inflammation and reconstruction of bronchus for controlling asthma. It has been approved that asthma is a polygene disease influenced by genetic variants and environment. Some controversy exist in the mechanism of asthma, including the role of eosinophils(EOS) in asthma.EOS is one of the effect cells in asthma. It has been proved that APC present antigen to surface of cell and result in the differentiation of Th2 that secrete cytokines, such as IL-4, IL-5 and IL-13. These cytokines facilitate CD34+ hematopoietic cell differentiate to EOS lineage in marrow. And then, the cells migrate from marrow to blood vessel induced by IL-5. VCAM-1, induced by IL-4 and IL-13 in endothelium, which band with receptor such as VLA-4 on the surface of EOS. So EOS can traverse vessel wall easily and recruit to the position of inflammation. The activated EOS act on all kinds of cells, such as fibroblast, muscle cells, epithelium, and secrete更多还原