内耳AVP-V2R-AQP2信号系统参与运动病作用与机制研究

运动病与梅尼埃病症状非常相似，且患者血液精氨酸加压素(AVP)水平均明显升高，静脉或脑室注入AVP可诱发人或动物产生恶心、呕吐等运动病症状。近年来的研究表明，梅尼埃病患者血浆AVP水平异常地增高，通过AVP-加压素受体(V2R)-水通道蛋白(AQP2)信号系统，使内耳AQP2表达升高，内淋巴液生成过多，导致膜迷路积水，从而诱发眩晕、恶心、呕吐等症状。我们前期的实验结果显示，诱发运动病的旋转刺激引起大鼠血浆AVP水平升高、内耳V2R、AQP2 mRNA与蛋白表达增加。因此，我们推测运动病与梅尼埃病发病机制存在相似之处，内耳AVP-V2R-AQP2信号系统的异常活动可能与运动病相关，参与了运动病发病过程，还可能与运动病敏感性个体差异相关。因此，本研究拟开展内耳AVP-V2R-AQP2信号系统与运动病相关性的研究，有助于弄清运动病发病机制，以便以此信号系统为靶点，研究开发新的抗运动病药物。

Motion sickness and Meniere's disease are much similar in symptomatology, both having an elevated level of arginine vasopressin (AVP) in blood, and intravenous or intracerebroventricular injection of AVP will induce motion sickness symptoms such as nausea and vomiting in humans or animals. Recent studies suggest that the plasma AVP level rises extraordinarily in human subject of Meniere's disease, causes high expression of aquaporin 2 (AQP2) in the inner ear via AVP-vasopressin receptor 2 (V2R)-AQP2 signal pathway, increases the production of endolymph, leads to endolymphatic hydrops, and eventually results in many symptoms such as vertigo, nausea and vomiting. Our preliminary results revealed that the plasma AVP level was elevated in rat after motion sickness-evoking rotatory stimulation, and the expression of V2R and AQP2 mRNA and protein were increased simultaneously. Thereby, we suppose that the underlying mechanism of motion sickness may be similar with that of Meniere's disease, i.e., abnormal activity of the inner ear AVP-V2R-AQP2 signal pathway may be also involved in the development of motion sickness and/or the individual difference in the susceptibility to motion sickness. Therefore, the present study is designed to investigate the relationship of the inner ear AVP-V2R-AQP2 signal pathway with motion sickness, so as to uncover the underlying mechanism of motion sickness, and find new targets aiming at this signal pathway for the development of drugs against motion sickness.