内耳Hensen细胞脂滴分解激活TLR4炎症通路参与噪声性损伤

Noise induced hearing loss (NIHL) is a priority disease in the public health disease which WHO defined and will greatly affect the daily life. The molecular pathogenic mechanism is still ambiguous and lacking effective treatment. That leads to the bottle neck of the treatment on NIHL. The inflammation pathway had been explored for years during the development of NIHL. Considering the special microenvironment in the scala media and the structure of Corti, the supporting cells may play an important role in the regulation of inflammation. This project starts with the innate structure of lipid droplets which is widely existed in Hensen cells. We designed series of in-vivo and ex-vivo experiments to testify the combination of the classic TLR4 inflammation pathway with the lipolysis under the condition of noise exposure. Futhermore, that connection would be involved in the development of NIHL and the innovative drug of lipolysis inhibitor would offer an entirely new treatment strategy by regulating the inflammation pathway. By that, it provide a new aspect to explore the pathogenic mechanism of NIHL and create an effective treatment strategy which would have a significance in the clinical treatment of NIHL.

噪声性耳聋是世界卫生组织明确的重点公共卫生疾病，严重影响患者生活质量。其致病机制尚无结论且缺乏有效治疗手段，使噪声性耳聋的治疗进入瓶颈。一些研究提示炎症通路参与噪声性耳聋的发病，由于中阶的结构特性，支持细胞对炎症反应的参与可能有重要作用。本项目从Hensen细胞中固有的脂滴这一特殊结构切入，创新提出强噪声条件下脂质分解产物可与经典的Toll样受体4(TLR4)结合，进而激活下游炎症通路，参与噪声性耳聋的损伤过程。利用动物模型分析噪声暴露后脂滴分解情况及中阶脂质微环境变化，通过离体、在体实验验证噪声暴露后脂解通路、TLR4通路的基因及蛋白质变化，揭示Hensen细胞脂质代谢在噪声损伤中的作用。继而提出利用脂质分解抑制剂进行药物干预，通过影响炎症反应降低噪声性损伤的全新防治策略。本项目的实现将为揭示噪声性耳聋的致病机制提供全新角度，更为其临床治疗提供新的可靠药物，具有重大的科研和临床意义。

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