咽喉部神经调控异常在阻塞性睡眠呼吸暂停-低通气综合征(OSAHS)发生中起重要作用.OSAHS不仅有吸气相上气道塌陷,严重时还有呼气相上气道闭塞.资料表明:中枢a2肾上腺素受体(a2-AR)激活可致间歇性呼气相声门关闭,产生呼气性窒息.该作用可能参与OSAHS发生,但中枢机制不明.本项目用逆行追踪法标记大鼠喉返神经节前神经元(PRLM);在具有呼吸节律的延髓脑片及脑桥-延髓标本,用膜片钳记录PRLM,以证明脑桥或延髓内a2-AR激活可选择性地在呼气相兴奋支配声门内收肌的呼气性PRLM.在大鼠脑桥去甲肾上腺素能神经核和/或延髓PRLM区域过表达a2A肾上腺素受体(a2A-AR),观察清醒和睡眠时呼吸节律;建立慢性间歇性缺氧型OSAHS模型大鼠,用免疫组织化学法观察脑桥和/或PRLM区a2A-AR表达,以证明脑桥和/或PRLM区a2-AR高表达或激活可致间歇性声门关闭和缺氧,进而参与OSAHS

Abnormal nervous control of the larynx and pharynx plays important roles in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS). Severe OSAHS is accompanied not only by inspiratory collapse but also by expiratory closure of the upper airway. It has been reported that activation of central alpha2-adrenoceptors results in intermittent expiratory closure of the glottis. This process may be involved in the pathogenesis of OSAHS, but the central mechanisms are unknown. In this project, preganglionic recurrent laryngeal motoneurons (PRLMs) are to be retrogradely labeled and studied in vitro with patch-clamp, in rhythmically active medullary and pon-medullary preparations, respectively. We aim to prove that activation of pontine and/or medullary alpha2-adrenoceptors can selectively excite expiratory PRLMs that innervate the adductor muscles of the glottis. Alpha2A-adrenoceptors (a2A-AR) are to be overexpressed in the pontine noradrenergic nuclei and the medullary PRLM-containing area, and the respiratory behavior during wakeness and sleep is to be monitored with plethysmography. OSAHS rat model is to be established by chronic intermittent hypoxia; and the expression of a2A-AR in the pontine noradrenergic nuclei and in the medullary PRLM-containing area is to be examined using immunohistochemistry. We aim to prove that overexpression and activation of alpha2-adrenoceptors in the pontine noradrenergic nuclei and the medullary PRLM-containing area contribute to the pathogenesis of OSAHS, via causing intermittent closure of the glottis and the resultant hypoxia.