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麻醉异氟烷或地氟烷加手术对阿尔茨海默病转基因小鼠的认知功能有不同影响。

Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer's Disease Transgenic Mice.

机构信息

Department of Anesthesia, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4310, Charlestown, MA, 02129-2060, USA.

出版信息

Mol Neurobiol. 2018 Jul;55(7):5623-5638. doi: 10.1007/s12035-017-0787-9. Epub 2017 Oct 6.

Abstract

Anesthesia/surgery could be associated with cognitive impairment and Alzheimer's disease neuropathogenesis. However, whether surgery under different anesthetics has different effects on cognitive function remains largely unknown. We therefore set out to compare effects of anesthetic isoflurane or desflurane plus surgery on cognitive function and hippocampus levels of synaptic marker (postsynaptic density-95 and synaptophysin) and ATP. Five-month-old AD Transgenic (Tg) (FAD5X) and wild-type male mice received isoflurane or desflurane plus abdominal surgery. We assessed cognitive function in Barnes maze and measured hippocampus levels of postsynaptic density-95, synaptophysin, and ATP in the mice. We determined whether vitamin K could mitigate these anesthesia/surgery-induced changes. Isoflurane, but not desflurane, plus surgery increased escape latency and escape distance in Barnes maze probe test and reduced postsynaptic density-95, synaptophysin, and ATP levels as compared to control condition in AD Tg mice. Vitamin K attenuated the anesthesia/surgery-induced changes in the AD Tg mice. These findings suggest that isoflurane, but not desflurane, plus surgery might induce cognitive impairment via causing brain energy deficits. Pending confirmative studies in both animals and humans suggest desflurane could be a better choice for AD patients when surgery is needed. Moreover, vitamin K could treat cognitive deficiency associated with anesthesia and surgery.

摘要

麻醉/手术可能与认知障碍和阿尔茨海默病神经发病机制有关。然而,不同麻醉下的手术是否对认知功能有不同的影响在很大程度上仍不清楚。因此,我们着手比较麻醉异氟醚或地氟醚加手术对认知功能和海马突触标记物(突触后密度-95 和突触小体)和 ATP 水平的影响。5 个月大的 AD 转基因(Tg)(FAD5X)和野生型雄性小鼠接受异氟醚或地氟醚加腹部手术。我们在 Barnes 迷宫中评估认知功能,并测量小鼠海马突触后密度-95、突触小体和 ATP 水平。我们确定维生素 K 是否可以减轻这些麻醉/手术引起的变化。与对照条件相比,异氟醚,但不是地氟醚,加手术增加了 AD Tg 小鼠在 Barnes 迷宫探测测试中的逃逸潜伏期和逃逸距离,并且降低了突触后密度-95、突触小体和 ATP 水平。维生素 K 减轻了 AD Tg 小鼠中麻醉/手术引起的变化。这些发现表明,异氟醚,但不是地氟醚,加手术可能通过引起大脑能量不足导致认知障碍。在动物和人类中进行的确认性研究表明,当需要手术时,地氟醚可能是 AD 患者的更好选择。此外,维生素 K 可以治疗与麻醉和手术相关的认知缺陷。

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