Navβ亚基调节Nav1.7异常表达参与周围神经电烧伤病理机制的研究

Dysfunction often occurred in peripheral nervous system after electrical burn, however the mechanism is still obscure. Dorsal root ganglia voltage-gated sodium channels are critically important for nociception, and the material basis of electrogenesis and nerve impulse conduction. In our previous research, the expression level of Nav1.7 is reduced after peripheral nervous electrical injury. It is suggested that Navβ subunit might regulate the expression and activity of Nav1.7, which is involved in mechanism of electrical injury to peripheral nervous. In this study, immunohistochemical, ethology, electrophysiological techniques and molecular biology technology and method are used to observe and detect the changes of pathological features, animal behavior, Nav1.7 and Navβ expression and location, and membrane electrical parameters. The purpose of our study is to investigate the regulation of Navβ to Nav1.7 expression and function, thereby the mechanism of electrical injury to peripheral nerve will be further revealed, and new potential drug target might be discovered based on the result of this project.

电烧伤后常伴有周围神经系统功能异常，但机制不清。背根神经节电压门控型钠离子通道在伤害性感受中起到重要作用，是神经冲动产生和传递的物质基础。我们前期的实验发现Nav1.7在电烧伤后表达水平下调，我们推测在离子通道蛋白复合体中Navβ亚基对Nav1.7的表达和活性起到调节作用，并参与了周围神经电烧伤的病理机制。基于此我们采用免疫组织化学技术、动物行为学、电生理技术和分子生物学技术着重观察电损伤后背根神经节神经元的病理改变，以及神经行为学的异常，在此基础上，对电损伤后背根神经节与感觉异常相关离子通道Nav1.7和Navβ亚基的表达、分布、膜电学参数变化进行检测，探索Navβ对Nav1.7表达和功能异常的调节作用，以及这种调节作用在周围神经电烧伤病理机制中的重要地位，力图为临床治疗提供新的治疗靶点。