术后认知功能障碍(POCD)以学习和记忆功能受损为重要表现，年龄是其重要危险因素。我们的前期研究和现有文献提示，"睡眠-觉醒"节律可在全麻药物的作用下发生偏移，年老导致的中枢昼夜起搏器振幅减少，褪黑素分泌下降等，可使"睡眠-觉醒"节律恢复延迟。偏移的睡眠节律可影响NR2B的节律性表达，从而通过影响其下游AMPAR和CREB的表达导致学习和记忆的改变。全麻后"睡眠-觉醒"节律长时期偏移可最终形成POCD。本研究将在小鼠皮下植入Mini Mitter及智能鼠笼检测芯片，于全麻下行普通开腹术，采用光照变化、噪音隔离、褪黑素干预及NR2B、AMPAR、CREB激动/拮抗等方法，检测不同年龄及处理下"睡眠-觉醒"节律及认知功能改变，采用行为学、分子生物学等技术，探讨NR2B-AMPAR/CREB在"睡眠-觉醒"节律长时期偏移与老年POCD之间的机制联系，为临床防治POCD提供新的思路。

Postoperative cognitive dysfunction (POCD) exhibits the impaired learning and memory as the major performance and age is one of the most important risk factors. Based on our previous studies and other research findings, we suggest that the sleep-wake rhythm could shift under general anesthesia, furthermore, the aging-induced amplitude reduction of central circadian pacemaker and the decreased secretion of melatonin may delay the reset of sleep-wake rhythm. The phase-shifting sleep-wake rhythm may affect the rhythmic expression of NR2B and finally change learning and memory via its downstream molecules AMPAR and CREB. Long-time phase-shifting sleep-wake rhythm after general anesthesia could finally result in POCD. In this study, we will subcutaneously implant the Mini Mitter and the microchip of Intellicage into mice and perform the laparotomy under general anesthesia. Daylight changes, noise isolation, melatonin intervention and agonistic or antagonistic NR2B/AMPAR/CREB will be used to detect changes of sleep-wake rhythm and cognitive function under different treatments in different ages. Behavioral and molecular biology techniques will be uesd to explore the role of NR2B-AMPAR/CREB in the crosstalk between long-time phase-shifting sleep-wake rhythm and POCD among the aged. This study will provide new ideas for the prevention and treatment of POCD.