梅尼埃病发病机制生物力学研究及临床应用

Ménière’s disease (MD) is a common inner ear disease, which causes symptoms of recurrent attacks of vertigo, fluctuating sensory hearing loss, etc., seriously disturbing the patients. However, the precise aetiology and pathogenesis remain unclear so that it confuses physicians to diagnose and treat MD. Naturally, it has become one of a worldwide challenge in the field of otolaryngology to make a better understanding and more effective treatment of MD. Some researchers claimed that the hydrostatic pressure produced by the endolymphatic hydrops may force either the Bast’s valve or the reuniens duct open, which cause a rapid fluid shunt and a sudden change in cochlear and vestibular function, then MD. In this project we will prove the inference using a biomechanical method. Specifically, we will establish a parallel biomechanical model combining with the theory and method of medicine and biomechanics based on the complete anatomy of the inner ear membranous labyrinth system to analyze the progress in endolymphatic hydrops and the pathogenesis of MD. Finally, by comparing the numerical results with the results of relevant animal experiments and clinical data, we will be able to reveal the pathogenesis of MD and develop a profound understanding of the mechanism of MD, and provide the foundation for researching the theory and practice of MD’s diagnosis, prevention, and treatment.

梅尼埃病（MD）为耳科一种常见疾病，其反复发作性眩晕和波动性感音神经性听力下降等症状严重困扰了患者。然而MD的病因和发病机理仍然不明确，其诊断和防治给医生带来了很大困惑，如何能够更好更有效的治疗MD是现今全世界耳鼻喉领域公认的难题之一。近年有学者推测MD的发病机理为：膜迷路积水产生的静水压力迫使闭合的Bast瓣膜或连合管突然张开，内淋巴体积重新分布，耳蜗和前庭功能突然变化，从而诱发出MD的症状。本项目将从生物力学角度对上述推测进行探索。具体方法是基于申请者前期内耳膜迷路有限元数值模型研究，应用医学与生物力学多学科交叉的方法，提取完整内耳迷路的解剖形态，建立膜迷路积水进程和MD发病机理生物力学研究平台，构建较完整内耳膜迷路有限元数值模型，结合相关动物实验和临床资料，从生物力学角度揭示MD的发病机理；加深人们和医生对MD发病机理的新的认识，为该病医学临床诊断和防治提供理论与实践研究基础。

梅尼埃病是一种以波动性听力下降和反复发作性眩晕为主要特征的特发性内耳疾病，到目前为止病因不明，临床以保守治疗为主。本课题采用生物力学方法对梅尼埃病的发病机理进行了研究。通过结合组织切片和micro-CT两种成像方法构建了豚鼠膜迷路数值模型。通过实验发现当膜迷路积水发生之后，使得内耳的听力功能下降，且推测Bast瓣膜这一结构突然张开是诱发梅尼埃病发作的原因。通过针对一例志愿者内耳膜迷路结构与功能关系进行有限元数值模拟发现：膜迷路积水致使Bast瓣膜张开，内耳膜迷路各部结构的内淋巴产生对流，使得半规管中的内淋巴产生流动和平衡感受器嵴顶发生变形和机电转导作用，诱发眩晕症状。膜迷路积水程度、积水发生的位置和Bast瓣膜的开口面积决定梅尼埃病发作的时长和眩晕的程度，此外，Bast瓣膜异常张开会导致膜迷路上部积水，膜迷路上部内淋巴流动增强，平衡感受器嵴顶的形变响应增强或减弱，影响半规管正常感受有角运动的能力。依据膜迷路积水致使内耳波动性听力下降的特点可用于梅尼埃病阈值的预测和预防。结合临床旋转试验和冷热试验定量诊断机制有希望进一步建立梅尼埃病精准评估模型，为梅尼埃病的预防、诊断和治疗提供理论依据。