电针通过Netrin-1/Unc5c/Caspase-3通路改善老龄大鼠较浅麻醉所致术后神经认知障碍的机制研究

术后神经认知障碍（PND）是老年患者术后常见且棘手的并发症之一，发病机理尚不清楚。术中麻醉深度不当是诱发PND的众多危险因素之一。我们前期临床和动物研究发现：1、较浅麻醉损伤术后认知功能，而较深麻醉显著减少PND的发生率；2、较浅麻醉可损伤细胞骨架F-actin而诱发PND；3、与药物相比，电针不仅可以缓解慢性疼痛症状，还可修复损伤的皮层神经元结构并纠正认知障碍。研究显示，电针等神经调控技术用于防治认知障碍优势显著，但用于防治较浅麻醉诱发的PND鲜有报道。基于文献和前期工作，我们假设"电针可通过Netrin-1/Unc5c/Caspase-3介导F-actin聚合，增强突触可塑性，从而防治较浅麻醉下手术诱发的PND”。本工作拟通过行为学、分子生物学、细胞成像及电生理等手段，首次对电针防治较浅麻醉损伤神经元细胞骨架的机制进行探索，为应对PND提供新策略。

Postoperative neurocognitive disorders (PND) are one of the most common complications during the postoperative period, however its pathogenesis is still not clear. Previous studies showed that inadequate depth of anesthesia can increase the incidence of PND in the patients undergoing surgery. Our previous researches on animal and human found that: (1) lighter anesthesia impaired cognitive function, while deeper anesthesia reduced the incidence of PND significantly; (2) PND induced by lighter anesthesia was associated with F-actin cytoskeleton disorganization; (3) electroacupuncture not only effectively alleviated pain, but also performed better than medications when repairing structural damages in cortical neurons and reversed cognitive impairment. It is reported that neuromodulation technologies such as electroacupuncture have a remarkable advantage in the treatment of cognitive dysfunction, while it has not been reported for preventing or treating PND induced by lighter anesthesia. Based on the literature reviews and our preliminary studies, we hypothesize that electroacupuncture enhances synaptic plasticity via Netrin-1/Unc5c/Caspase-3-mediated F-actin polymerization, thereby alleviating PND caused by lighter anesthesia. We intend to explore the mechanisms of electroacupuncture for prevention and treatment of PND induced by lighter anesthesia via behavioral tests, molecular biological methods, cell imaging and electrophysiological techniques, providing new evidence in coping with PND.