NGF/TrkA通路在颈椎退变诱发交感神经症状中的作用和机制研究

The mechanism of cervical degeneration causing sympathetic symptoms is the key point in revealing the pathogenesis of Cervical spondylosis myelopathy (CSM) accompanied with sympathetic symptoms. Our previous study found that the posterior longitudinal ligament (PLL) in the degenerative level may play a significant role in the pathological process of cervical degeneration causing sympathetic symptoms. Further research found there is a connection between the neuron activity in cervical sympathetic ganglion(CSG) caused by cervical degeneration and nerve fibers distributed in PLL. But the pathway and regulate mechanism of such pathological process is unclear. Based on the results of research in the last Natural Science Foundation and the phenomenon found in the preliminary experiments, we make a hypothesis that cervical degeneration can excite the sympathetic fibers in PLL and stimulate neuron activity in the corresponding CSG by NGF/TrkA pathway, and then cause sympathetic symptoms. In animal models, we will regulate the key protein expression in NGF/TrkA passway to investigate its effect on cervical sympathetic ganglion in PLL. We aim to clarify the role and mechanism of NGF/TrkA passway in cervical degeneration causing sympathetic symptoms.

颈椎退变诱发交感神经症状的机制是揭示伴交感神经症状颈椎病致病原因的关键问题。课题组前期研究证实，颈椎后纵韧带（PLL）上交感神经节后纤维是颈椎退局部病理刺激诱发交感神经症状的重要“调节阀”。进一步研究发现：颈椎退变后PLL上交感神经节后纤维逆行增强颈交感神经节（CSG）神经元活动，导致诱发不同的交感神经症状，而这一效应可能与PLL上交感神经纤维异常增生有关，但其产生和调节机制尚不清楚。我们提出假设：颈椎持续病理刺激过度激活局部PLL上的交感神经末梢，通过NGF/TrkA通路影响交感神经末梢芽生，从而激发相应CSG神经元活动引发交感神经症状。本课题拟以前期建立的动物模型为载体，通过分别观察和干预NGF/TrkA通路信号分子的变化对PLL上交感神经末梢芽生的影响，进一步阐明该通路在颈椎退变诱发交感神经症状中的作用和机制，为明确判定“责任间隙”提供实验依据。

课题以前期研究证实的颈椎后纵韧带（PLL）是颈椎退变导致交感神经症状发生的关键因素为基础，探索颈椎退变间隙通过NGF/TrkA通路影响对应CSG神经元增生的机制。课题通过比格犬颈椎退变压迫后纵韧带的可靠实验动物模型，利用生物信号采集、电生理检测和分子生物学技术开展研究。结果发现：1、存在颈椎退变病理因素持续刺激的间隙是引发交感神经症状的“责任间隙”，慢性病理刺激下该间隙处PLL上交感神经纤维增生可增强相应CSG神经活动；2、造模节段对应交感神经节上NGF、TrkA蛋白表达水平明显增高，存在椎节失稳的条件下，上述通路信号的表达更为明显;3、NGF/TrkA通路在PLL引发SCG神经元活动中发挥调节作用，拮抗干预该通路可显著影响SCG神经元的电生理活动。上述实验结果证实了本课题的初步设想：颈椎不稳等持续病理因素可刺激退变间隙处局部PLL上的交感神经末梢，通过NGF/TrkA通路激发对应颈交感结（CSG）神经纤维增生、电活动活跃。抑制NGF/TrkA通路上下游信号因子的表达，可有效调控“目标”CSG 电生理活动。初步阐明了该通路在颈椎退变诱发交感神经症状中的作用和机制，为明确判定致病“责任间隙”、寻找早期机制性治疗的方法提供了实验依据。