针刺调节皮质-孤束核环路对中风后吞咽障碍模型动物干预作用的研究

Cortex-solitary nucleus loop is critical to the initiation of the spontaneous swallowing process. Damage to the loop caused by the stroke results in inhalation pneumonia which is the most serious complication of dysphagia. The therapeutic effect of modern medicine in the treatment of dysphagia is not clear. A large number of studies have shown that acupuncture at Lianquan (CV23) has a good clinical effect on post-stroke dysphagia, and many classical literatures have recorded the experience of using Lianquan (CV23) to treat dysphagia. But the effect of acupuncture at Lianquan (CV23) in animal model of post-stroke dysphagia has not been described. On the basis of previous study which showed that acupuncture at Lianquan (CV23) can affect the cortical and solitary nucleus activity in the physiological state, this study was based on the classical theory of acupuncture described with “Hard to swallow, CV23 selected” and propose cortex-solitary nucleus loop as the breakthrough point, with application of new technologies such as neurotropic virus markers, fiber optic recording and two-photon microscopy imaging, to carry out a systematic research on the effect of acupuncture on cortex-solitary nucleus loop in animal model of post-stroke dysphagia, to reveal the neurobiological mechanism of acupuncture treatment in post-stroke dysphagia, and to provide a reliable experimental evidence for acupuncture at Lianquan (CV23) to treat post-stroke dysphagia in the clinical practice.

皮质-孤束核环路对自主吞咽过程的启动至关重要，中风导致的皮质-孤束核环路受损所引起的吸入性肺炎是吞咽障碍最严重的并发症。现代医学治疗吞咽障碍的疗效不确切，大量研究表明针刺廉泉穴对中风后吞咽障碍有着较好的临床疗效，且诸多古代经典文献均有记载运用针刺廉泉穴治疗吞咽障碍的经验，但在针刺廉泉穴治疗中风后吞咽障碍动物模型的实验研究方面则未见报道。在本课题组前期研究表明生理状态下针刺廉泉穴可以影响皮质和孤束核活动的基础上，本研究基于“下食难，取廉泉”的针灸经典理论，以吞咽的皮质-孤束核环路为切入点，应用嗜神经病毒标记，在体光纤记录，双光子显微成像等新兴技术，系统研究针刺调节皮质-孤束核环路对中风后吞咽障碍模型动物的干预作用，揭示针刺治疗中风后吞咽障碍的神经生物学机制，为临床开展针刺廉泉穴治疗中风后吞咽障碍提供真实可靠的实验依据。

对于卒中后吞咽困难(PSD)的治疗，吞咽训练、咽电刺激、经颅磁刺激在临床应用广泛。刺激穴位用于治疗各种疾病已有2500多年的历史，而刺激位于舌骨上方凹陷的廉泉穴(CV23)则有助于治疗吞咽障碍。然而，对这种传统治疗的神经生物学机制知之甚少。通过逆行追踪，我们在鼠的初级运动皮层(M1)第5层发现了一簇控制下颌舌骨肌的神经元，这是吞咽过程中被激活的初始肌肉。通过光遗传学激活这些神经元可诱导下颌舌骨肌的电位。此外，小鼠的CV23刺激可改善M1缺血后的饮水能力和下颌舌骨电位。值得注意的是，无论是在CV23刺激期间还是之后，未受损半球的M1 L5兴奋性神经元都被激活，而沉默这些神经元阻止了CV23刺激驱动的吞咽功能改善。此外，经证实，孤束核(NTS)参与M1缺血后的吞咽。经逆行狂犬病毒(RV)示踪鉴定M1-NTS的吞咽神经结构回路，证实其参与了M1缺血后电刺激CV23特异性区域的调节过程。总之，这些结果揭示了精确的咽穴位CV23的电刺激可以影响M1及其下游皮层下回路的兴奋性，从而有助于PSD后的神经康复。