咽鼓管功能障碍可使咽鼓管开放受限、炎症清除能力下降进而导致分泌性中耳炎，但具体机制仍不清楚。我们前期研究发现SP-A在分泌性中耳炎小鼠咽鼓管的表达显著高于正常咽鼓管。我们推测SP-A可能通过参与咽鼓管的功能调节进而影响中耳炎的发生。本研究拟在此基础上，利用SP-A基因敲除小鼠制作分泌性中耳炎模型，研究SP-A缺失情况下，咽鼓管功能变化，再以外源性SP-A干预，反向验证SP-A对咽鼓管的影响；动态检测SP-A的表达与炎性细胞因子TNF-Α、IL-6和 IL-1β表达的关系，阐明SP-A影响咽鼓管功能异常的炎症机制。以SP-A干预RAW264.7巨噬细胞检测迁移、吞噬功能变化，对比吞噬功能信号分子Rho家族GTP酶亚家族蛋白Rho、Rac、Cdc42的表达变化，验证SP-A影响巨噬细胞功能的具体分子机制；阐明SP-A对咽鼓管扩张和清除功能的影响机理，为治疗分泌性中耳炎提供新思路。

The eustachian tube dysfunction could restrict eustachian tube opening, weaken inflammation clearance, which might cause otitis media with effusion. The detail mechanism is still unknown. Our previous study proved that the expression of SP-A in eustachian tube of otitis media with effusion mice was obviously higher than that in normal mice, which indicated that SP-A might regulate the function of eustachian tube involving otitis media with effusion. This study will compare the changes of the function of the eustachian tube between the SP-A gene knock out mice and the wild type mice with otitis media with effusion. Exogenous SP-A is injected into the middle ear for otitis media with effusion，which is used to identify the effect of SP-A on the function of eustachian tube from the opposite direction. Dynamic detection will be made for the expression of SP-A, TNF-Α, IL-6 and IL-1β to identify the possible inflammatory mechanism which SP-A effects on the function of the eustachian tube. This study will also detect the changing of phagocytosis and migration function of RAW 264.7 macrophage after the intervention with different concentrations of SP-A. The expression activity of phagocytosis-related Rho family GTP enzyme including Rho, Rac, Cdc42 will be detected to identify the detailed mechanism. This study might provide the new strategy to treat otitis media with effusion.