Li Guohua, Wang Yu, Cao Fang, Wang Dawei, Zhou Limin, Jin Yanwu
Department of Anesthesiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.
Department of Orthopedics, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.
Front Neurosci. 2021 Dec 2;15:647136. doi: 10.3389/fnins.2021.647136. eCollection 2021.
Sevoflurane (SEVO) is a highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for general anesthesia. Previous studies have shown that SEVO may induce impaired memory and recognition ability and may be associated with neurodegenerative disease, e.g., Alzheimer's disease (AD). However, the underlying mechanism remains unknown. Here, we used a mouse AD model, APP/PS1, to study the effects of SEVO on neurodegeneration occurring in AD. We found that SEVO exposure significantly impaired the spatial reference memory, sensorimotor, and cognitive function of the mice. Mechanistically, we found that SEVO induced formation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and its downstream caspase 1-mediated production of IL-1β and IL-18, which subsequently deactivated brain-derived neurotrophic factor (BDNF) to promote neurodegeneration. Together, these data suggest that NLRP3 inflammasome is essential for SEVO-induced AD.
七氟醚（SEVO）是一种高度氟化的甲基异丙基醚，用作全身麻醉的吸入性麻醉剂。先前的研究表明，SEVO可能会导致记忆和识别能力受损，并可能与神经退行性疾病有关，例如阿尔茨海默病（AD）。然而，其潜在机制仍然未知。在此，我们使用小鼠AD模型APP/PS1来研究SEVO对AD中发生的神经退行性变的影响。我们发现，暴露于SEVO会显著损害小鼠的空间参考记忆、感觉运动和认知功能。从机制上讲，我们发现SEVO诱导含NOD、LRR和pyrin结构域蛋白3（NLRP3）炎性小体的形成及其下游半胱天冬酶1介导的IL-1β和IL-18的产生，随后使脑源性神经营养因子（BDNF）失活以促进神经退行性变。总之，这些数据表明NLRP3炎性小体对于SEVO诱导的AD至关重要。
