一侧膈神经上根联合颈袢甲舌肌支选择性神经再支配喉外展及内收肌的实验研究

Bilateral vocal fold paralysis caused by bilateral recurrent laryngeal nerve (RLN) injury is a life- threatening condition because it could cause dyspnea, and even asphyxia. The traditional treatments are not optimal because it usually worsens the vocal function and causes aspiration. So far there is not any effective surgical procedure which can recover the adductive and abductive function of the bilateral paralyzed vocal cord simultaneously. We have achieved success both in restoring the adduction function using ansa cervicalis and restoring the abduction function using phrenic function, respectively. Based on our experience and the literature, the present concurrent repair procedure of adductive and abductive branches of RLN is not successful mainly due to the misdirected regeneration. We assumed that misdirected regeneration could be avoided by selective reinnervation through phrenic nerve and ansa cervicalis, and by making the regenerating axons from the two nerves arrive at their target laryngeal muscles synchonously. In the present study, we presented the new surgical procedure, i.e. concurrent selective laryngeal reinnervation using phrenic nerve and ansa cervicalis branches, in which we used a “Y” shape graft bridging between the right phrenic nerve and bilateral recurrent laryngeal nerves, comined with free nerve grafts from cervical plexus bridging between bilateral thyrohyoid branch of ansa cervalis and adductor branch of RLN, making sure that the path between the two nerves and their target muslces are similar in length. At different time points postoperatively, we are planning to observe bilateral vocal cord function through endoscopy, electrophysiological examination, histological examination of laryngeal muscles and regenerated nerve, double staining of synaptophysin and AchR in nerve muscle junction, and heavy myosin chain examination of reinnervated laryngeal abductor and adductor muscles, and fluorescent retrograde tracing, to evaluate the degree of misdirected regeneration by the above-stated different methods. We are hoping to demonstrate that this new surgical procedure could recover the adductive and abductive function of bilateral vocal folds to a satisfactory degree, and shed light on the further clinical application of this new surgical procedure.

双侧喉返神经损伤严重影响患者的生活质量甚至窒息危及生命，现有手术方法加重声嘶，引起呛咳误吸。联合神经修复外展及内收功能的手术至今效果不佳，我们在分别采用颈袢或膈神经修复喉返神经单纯恢复内收或外展功能取得成功的基础上，结合文献分析现有联合修复方法由于神经的错向再生致使手术失败。我们推测通过二种替代神经的选择性联合神经修复，同步再神经支配相应靶肌肉，可以避免神经错向再生。为此，我们提出一侧膈神经上根和颈袢甲舌肌支联合选择性神经再支配喉外展及内收肌，桥接自体神经保持再生神经的长度一致。通过术后不同时间点的声带运动观察、神经电生理检测、神经肌肉形态学分析、神经肌肉接头突触素和乙酰胆碱受体双标评价二种再生神经纤维是否同步支配靶肌肉；结合荧光逆行追踪运动神经元中枢定位，评价二种神经的错向再生程度。证实该联合神经修复新方案能使双侧声带恢复生理性外展及内收运动，从而为临床应用提供理论基础和实验依据。

双侧喉返神经损伤严重影响患者的生活质量甚至窒息危及生命，现有手术方法加重声嘶，引起呛咳误吸。联合神经修复外展及内收功能的手术至今效果不佳，我们在分别采用颈袢或膈神经修复喉返神经单纯恢复内收或外展功能取得成功的基础上，结合文献分析现有联合修复方法由于神经的错向再生致使手术失败。我们推测通过二种替代神经的选择性联合神经修复，同步再神经支配相应靶肌肉，可以避免神经错向再生。为此，我们提出一侧膈神经上根和颈袢甲舌肌支联合选择性神经再支配喉外展及内收肌，桥接自体神经保持再生神经的长度一致。本研究中，我们建立了膈神经联合颈袢神经甲舌肌支神经再支配喉外展及内收肌的比格犬动物模型，并于术后不同时间点的声带运动观察、神经电生理检测、神经肌肉形态学分析，评价损伤侧声带运动功能的恢复程度，以及有无错向再生。本研究证实该联合神经修复新方案能使双侧声带恢复生理性外展肌内收运动，从而为临床应用提供理论基础和实验依据。