摘要
背景 : 临床前和临床证据表明，老年人在全身麻醉后认知能力下降的风险增加。全身麻醉也被认为是术后认知功能障碍（POCD）和阿尔茨海默病（AD）的危险因素。在动物研究和小型临床试验中，通过鼻内注射胰岛素，直接将药物输送到大脑，能够改善记忆和认知能力。然而，胰岛素治疗改善认知功能的机理鲜为人知。 方法: 麻醉前用鼻内胰岛素或生理盐水对老龄小鼠进行预处理。胰岛素/生理盐水治疗第7天开始，将异丙酚腹腔注射给小鼠，维持全麻2小时/天，连续5天。小鼠继续胰岛素或生理盐水给药15天，第26天评估小鼠。. 结果: 研究发现，如新物体识别测试和情境依赖性恐惧调节测试所测试的，鼻内胰岛素治疗可预防麻醉引发的认知障碍。胰岛素治疗还增加了海马齿状回突触后密度蛋白95（PSD95）的表达，以及上调的微管相关蛋白2（MAP-2）。此外，我们发现胰岛素治疗通过激活PI3K/PDK1/AKT通路恢复了麻醉引起的胰岛素信号传导紊乱，并减弱了麻醉诱导的多个AD相关部位tau的高磷酸化。我们发现，通过增加Ser9处磷酸化的GSK3β水平，tau超磷酸化减弱，导致GSK-3β失活。 结论: 鼻腔注射胰岛素可能是预防老年人麻醉引发的认知障碍的一种有效治疗方法。
关键词: 术后认知功能障碍（POCD），胰岛素，丙泊酚，tau高磷酸化，认知障碍，记忆缺陷。
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