术后认知功能障碍（POCD）是老年患者全麻术后常见并发症，其临床表现与早期阿尔兹海默症（AD）相似，但确切分子机制不明。既往研究表明，Aβ可减少突触膜上CaMKII。同时，我们预实验发现，雷帕霉素（RAPA）可逆转七氟烷破坏的“自噬流”并减少AD模型小鼠海马Aβ聚集；纳米C60可增加突触CaMKII。我们推测：七氟烷破坏“自噬流”致胞内Aβ积累，进而减少突触CaMKII可能是其诱导POCD的分子机制；而C60载RAPA药物可通过上调自噬和突触CaMKII改善七氟烷诱导的POCD。本课题拟以七氟烷为模式药，通过Morris水迷宫检测老年小鼠空间记忆水平变化；通过IF、WB、ELISA等检测七氟烷对“自噬流”、Aβ水平的影响；通过增加或清除Aβ探讨七氟烷所致Aβ积累与突触CaMKII水平的关系；最后，检测C60-RAPA能否改善POCD，以期为POCD提供新的防治策略。

Postoperative cognitive dysfunction (POCD) is a common complication after general anesthesia and surgery in elderly patients, whose clinical manifestations are similar to those of Alzheimer's disease (AD). But its mechanism is not clear. Previous studies have shown that Aβ accumulation can reduce the synaptic CaMKII. Applicants have previously found that rapamycin (RAPA) reverses sevoflurane-blocked "autophagic flux" and decreases Aβ aggregation in the hippocampus, and C60 increase CaMKII transport to synapses. We hypothesize that sevoflurane disrupts “autophagic flux” leading to the accumulation of intracellular Aβ, and the decrease of synaptic CaMKII caused by accumulated Aβ may be the molecular mechanism of POCD; while C60-RAPA drugs may improve general anesthetics-induced POCD by upregulating autophagy and increasing synaptic CaMKII levels. Using sevoflurane as the model anesthesia, this project intends to test mice cognitive function change by Morris water maze, to detect the effect that sevoflurane on "autophagy flux" and Aβ levels by IF, WB, ELISA, to explore the relationship between Aβaccumlation and synaptic CaMKII by adding or clearing Aβ. Finally, we investigate whether C60-RAPA can block sevoflurane-induced POCD, and expect to provide new strategies for the prevention and treatment of POCD.