细胞谱系示踪技术研究基底细胞在中耳纤毛上皮损伤修复中的作用及机制

急性化脓性中耳炎损伤的纤毛上皮可迅速恢复正常，而慢性化脓性中耳炎状态则存在中耳纤毛上皮修复障碍，目前对急慢性化脓性中耳炎截然不同的上皮转归机制认识不清楚。气道上皮的研究表明基底细胞（Basal cells,BCs）分化再生是纤毛上皮损伤修复的重要机制，且基于申请人前期利用细胞谱系示踪技术研究发现中耳BCs具有分化再生的潜能，本项目拟进一步深入的研究BCs是否在中耳纤毛上皮损伤修复中起关键作用，从而介导急慢性化脓性中耳炎截然不同的上皮转归。本研究拟使用mT/mG+/+;K5CreERT2+/-转基因小鼠，通过中耳注射肺炎链球菌诱发急慢性化脓性中耳炎，利用细胞谱系示踪技术在遗传水平确认BCs在中耳纤毛上皮损伤修复中的作用；并通过检测BCs的增殖分裂、分化再生功能，在细胞水平揭示BCs介导慢性化脓性中耳炎纤毛上皮修复障碍的机制，为将来深入研究其分子机制及干预BCs增殖分化提供研究依据及方向。

The mechanism that the ciliated epithelium was self-healing in the condition of acute suppurative otitis media while cannot repair themselves in the condition of chronic suppurative otitis media was not clear. Basal cells (BCs) in the airway mediate the repair of airway epithelium via proliferation and regeneration. We have confirmed with cell lineage tracing technology that BCs of middle ear had the capacity of differentiation and regeneration. This project intends to further investigate whether BCs play a role in the repair of ciliated epithelial of the middle ear under pathological conditions, thus mediating the distinct epithelial outcomes of acute and chronic suppurative otitis media. In this study, we plan to induce acute and chronic suppurative otitis media by injecting streptococcus pneumoniae type 14 into the middle ear with mT/mG+/+;K5 Creert2+/- transgenic mice. The proliferation and differentiation function of BCs in pathological state will be detected at the genetic level to clarify the important role of BCs in the repair of ciliary epithelia in the middle ear. This study intends to reveal the mechanism of repair failure of ciliary epithelial in the condition of chronic suppurative otitis media, and to provide new ideas and directions for the study of molecular mechanisms for further interfering the proliferation and differentiation of BCs.