通咽喷雾剂对舌神经肌肉兴奋性干预效应及机制研究

Clinical researches in the early stage have confirmed that the effect of the external use of Tongyan Spray (consists of ginger, clematis radix, etc) on oral cavity and pharynx for stroke-induced dysphagia is well established.However, up to now, no animal model of dysphagia has been made,which hinders the relevant pharmacodynamics study.Tongyan Spray mainly affects oropharyngeal region,involving important deglutition muscle-lingualis,and deglutition related nerves,such as hypoglossal nerve,lingual nerve, glossopharyngeal nerve and vagus nerve.From the angle of neuroelectrophysiology,this study is to destroy lingual and hypoglossal nerves by pressing method, after the administration of Tongyan Spray,observe the effect of the drug on excitability and contraction in rat lingualis ,as well as that on evoked potential which can reflect conduction function of lingual nerve.Determine the concentration of excitable neurotransmitters acetylcholine(ACh) and nitrogen monoxide(NO)in hypoglossal nuclei, deglutition related transmitter 5-hydroxy tryptamine(5-HT) and glutamic acid(Glu) in solitary nucleus of medulla oblongata,nerve repair transmitter calcitonin gene related peptide(CGRP) , and compare that with the sham operation group,the model group and the normal saline group.The purpose of the study is to investigate the mechanism of Tongyan Spray on the post-stroke dysphagia patients at the deeper level,lie the foundation of further investigating for and using of this drug,and provide a reference way to assess drugs for treating dysphagia.

本项目前期临床研究证实通咽喷雾剂（含生姜、威灵仙等）口咽部外用，治疗脑卒中后吞咽困难疗效肯定。因目前尚无吞咽困难动物模型，故难以开展相关药效学研究。口咽部是通咽喷雾剂临床主要用药部位，涉及重要吞咽肌-舌肌及舌下神经、舌神经、舌咽神经、迷走神经等吞咽相关神经。本研究拟从神经电生理角度切入，采用压榨法损伤舌神经与舌下神经，舌咽部给药通咽喷雾剂，检测该药对大鼠在体舌肌兴奋收缩功能的影响，对反应舌神经传导功能的诱发电位的影响。测定舌下神经核内兴奋性递质乙酰胆碱（ACh）、一氧化氮（NO），舌咽神经、迷走神经上行核团-延髓孤束核内吞咽相关递质五-羟色胺（5-HT）、谷氨酸（Glu）以及神经修复递质降钙素基因相关肽(CGRP)浓度的变化，并与假手术组、模型组、生理盐水组相比较。旨在探讨通咽喷雾剂改善吞咽功能的深层次作用机制，为后续开发应用研究打下基础，并为同类研究提供可以借鉴的吞咽困难药物评价方法。

本项目前期临床研究证实通咽喷雾剂(含生姜、威灵仙等)口咽部外用，治疗脑卒中后吞咽障碍疗效肯定。本研究从神经电生理角度切入，采用压榨法损伤舌神经与舌下神经，舌咽部给药通咽喷雾剂，检测该药对大鼠在体舌肌兴奋收缩功能的影响，舌神经传导功能的诱发电位的影响。测定舌下神经核内兴奋性递质乙酰胆碱(ACh)、一 氧化氮(NO)，舌咽神经、迷走神经上行核团-延髓孤束核内吞咽相关递质五-羟色胺(5- HT)、谷氨酸(Glu)以及神经修复递质降钙素基因相关肽(CGRP)浓度的变化。研究结果表明该药对早期损伤的舌下神经运动传出途径作用不明显，但可改善线栓法短暂性阻塞大脑中动脉大鼠的吞咽功能，其作用机制可能与增加血清SP及孤束核内SP与5-HT含量，激活辣椒素敏感类神经纤维有关。钳夹舌下神经后，通咽喷雾剂通过降低舌肌的阈强度，提高舌肌的收缩幅度来改善舌下神经损伤后带来的吞咽障碍；与此同时，舌下神经核内5-HT、ACh等运动相关递质明显增加，促进神经元的恢复，从而减缓吞咽困难。本研究达到了预期目标，为后续开发应用研究打下基础，并为同类研究提供可以借鉴的吞咽困难药物评价方法。

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