PB/PC核群介导谷氨酸调节EEG微觉醒发生的机制研究

微觉醒是睡眠呼吸事件发生时脑电发生的去同步化改变，可导致睡眠片段化。二氧化碳是睡眠呼吸暂停发生时引起微觉醒反应的主要刺激因子之一。PB复合体是连接脑干氧感觉系统和前脑，以及脑干微觉醒通路的重要桥梁。本课题以PB/PC核群为研究对象，应用野生型和vGluT2基因敲除小鼠，观察间歇反复二氧化碳增高时，PB/PC核群活性的改变。进一步应用CTB逆向示踪技术，确定PB/PC与微觉醒相关中枢部位及调节上气道肌肉活动的中枢核团的联系。Fos蛋白表达结合逆向示踪技术和vGluT2原位杂交方法，证明谷氨酸是PB/PC和上述核团联系的主要神经递质。PB/PC核团注射谷氨酸受体拮抗剂，比较野生型和vGluT2基因特异性敲除小鼠脑电微觉醒阈值和颏舌肌肌电活性的不同。阐明PB/PC核团的谷氨酸通路在调节微觉醒中的重要地位，为睡眠呼吸暂停的临床治疗提供理论依据。

Arousal is a desynchronized change of EEG during sleep breathing events, which can lead to sleep fragmentation. Carbon dioxide (CO2) is one of the main stimulants that induce arousal during sleep apnea. PB complex is an important site connecting brainstem oxygen sensory system and forebrain, as well as brainstem arousal pathway. In this study, we focus onPB/PC nuclear group. Wild type and vGluT2 knockout mice were used to observe the changes of PB/PC nuclear group activity when intermittent and repeated increase of carbon dioxide. The relationship between PB/PC and arousal-related central sites and the central nuclei regulating upper airway muscle activity was further determined by CTB reverse tracing technique. Fos protein expression combined with reverse tracing and vGluT2 in situ hybridization proved that glutamate was the main neurotransmitter associated with PB/PC and the above nuclei. PB/PC nuclei were injected with glutamate receptor antagonists to compare the EEG arousal threshold and genioglossal myoelectrical activity of wild type and vGluT2 gene-specific knockout mice. To clarify the important role of glutamate pathway of PB/PC nuclei in regulating arousal, and to provide theoretical basis for clinical treatment of sleep apnea.