睡眠片段化导致抑制控制障碍诱发非饥饿摄食行为及其神经机制研究

肥胖防治对于阻塞性睡眠呼吸暂停（OSA）患者的预后改善意义重大。非饥饿摄食是导致肥胖的重要原因，是指在非饥饿条件下、因中枢享乐驱动而产生的过量摄食行为。既往研究显示，前额叶皮层（PFC）神经元受损引起的抑制控制障碍是非饥饿摄食的主要机制之一。新近临床研究提示，在同等条件下、OSA患者更易于出现非饥饿摄食，但发生机制不明。我们预实验发现，OSA患者的睡眠片段化与非饥饿摄食密切相关；进一步的磁共振成像及认知评估发现，OSA患者的背外侧PFC体积减小，并伴有抑制控制障碍表现。为此，我们提出假说，睡眠片段化通过损伤背外侧PFC，导致抑制控制障碍，诱发非饥饿摄食行为。本课题拟联合临床及动物实验，明确睡眠片段化对抑制控制能力及非饥饿摄食行为的影响；应用磁共振波谱分析、膜片钳神经元电生理等技术，探索睡眠片段化所致神经损伤的机制。申报项目有望为OSA患者非饥饿摄食行为的纠正、肥胖防治新手段的开发提供依据。

The prevention and treatment of obesity is vital for the prognosis in patients with obstructive sleep apnea (OSA). Hedonic eating is an important cause of obesity, which refers to overeating behaviors driven not by metabolic need but by the reward experienced by consuming the food. Previous studies showed that the inhibitory control impairment, a consequence of damage to the prefrontal cortex (PFC) neurons, plays a crucial role in the pathogenesis of hedonic eating. Recent clinical studies suggested patients with OSA tend to exhibit hedonic eating as compared to their counterparts, but the mechanism is still unknown. Our preliminary study found that sleep fragmentation is closely related to hedonic eating in OSA patients. With brain magnetic resonance imaging and cognitive tests, we further observed a reduced dorsolateral PFC volume, as well as an impaired inhibitory control for OSA patients as compared to their counterparts. Therefore, we put forward the hypothesis that sleep fragmentation leads to damages in dorsolateral PFC and causes inhibitory control impairment, which further contributes to the pathogenesis of hedonic eating. The aim of the current research is to explore whether sleep fragmentation could lead to adverse changes in inhibitory control and hedonic eating behaviors, in both clinical and animal experiments. Furthermore, with laboratory techniques including magnetic resonance spectroscopy, patch-clamp electrophysiology and etc., we aim to clarify the neuromechanism underling these adverse changes. This research will provide novel insights into the correction of hedonic eating behaviors, as well as the prevention and treatment of obesity for patients with OSA.