呼吸调控环路增益（Loop Gain，LG）增高、呼吸调控不稳是阻塞性睡眠呼吸暂停（OSA）的重要病理基础，但其分子机制尚未完全阐明。本项目基于前期高迁移率族蛋白B1（HMGB1）介导OSA相关炎症损伤参与呼吸调控的研究基础，提出科学假说：长期间歇低氧可激活中枢HMGB1通路产生促炎因子IL-1β，进而抑制中枢化学感受器分子TASK-1通道开放引起呼吸中枢敏感性增强、LG增高，从而引起OSA。为此我们建立间歇低氧大鼠模型，在动物实验中研究间歇低氧对环路增益及HMGB1/IL-1β通路激活的影响；在膜片钳实验中揭示IL-1β对脑干神经元TASK-1电流影响；进一步通过小胶质细胞和脑干神经元共培养，给予HMGB1抑制剂、观察炎症因子表达及神经元兴奋性变化。研究成果将阐明HMGB1介导中枢炎症损伤参与OSA高LG的分子机制，深化OSA的炎症发病机制认识，为OSA抗炎治疗药物研发提供新思路。

The high loop gain (LG) of respiratory control contribute to the occurrence of sleep apnea, but its molecular mechanism has not been fully elucidated. Based on the former research foundation that the central inflammation induced by high mobility group protein B1 (HMGB1) participating respiratory control, we puts forward the scientific hypothesis: long term intermittent hypoxia can activate HMGB1 pathway and produce pro-inflammatory factor IL-1 β, whose inhibit the central chemoreceptor molecule TASK-1 and in turn cause the increase of LG and result in OSA. Therefore, we established a rat model of intermittent hypoxia, and studied the effects of intermittent hypoxia on loop gain and activation of HMGB1 / IL-1 β pathway in animal experiments. The effects of IL-1 β on the TASK-1 current of brain stem neurons were revealed by patch clamp experiments. Further, through co culture of microglia and brain stem neurons, we observed the expression of inflammatory factors and the changes of neuronal excitability by interfering HMGB1 signal pathway. The research results will clarify the molecular mechanism of HMGB1 mediated central inflammation involved in OSA high LG, and provide new ideas for the understanding of the pathogenesis of OSA.