Activation of autophagy inhibits the activation of NLRP3 inflammasome and alleviates sevoflurane-induced cognitive dysfunction in elderly rats

作者：Junjie Zhou, Chao Zhang, Xu Fang, Naixin Zhang, Xiaoxi Zhang, Zhaoqiong Zhu · 发表于：BMC Neuroscience · 年份：2023 · DOI：10.1186/s12868-023-00777-5 · 被引用次数：33 · 研究领域：Intensive Care Unit Cognitive Disorders、Anesthesia and Neurotoxicity Research、Tryptophan and brain disorders

AIMS/INTRODUCTION: As a common complication in elderly patients after surgery/anesthesia, postoperative cognitive dysfunction (POCD) is mainly characterized by memory, attention, motor, and intellectual retardation. Neuroinflammation is one of the most uncontroversial views in POCD. The sevoflurane-induced neurotoxicity has attracted widespread attention in recent years. However, its mechanism has not been determined. This study aimed to observe the effects of sevoflurane on cognitive function and the changes in inflammatory indices and autophagy protein expression in the prefrontal cortex in aged rats. METHOD: Before the experiment, D-galactose was diluted with normal saline into a liquid with a concentration of 125 mg/kg and injected subcutaneously into the neck and back of rats for 42 days to establish the aging rat model. Morris water maze experiments were performed, including positioning navigation (5 days) and space exploration (1 day). The POCD model was established by 3.2% sevoflurane inhalation. The rats were treated with or without MCC950, a potent and selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inhibitor, followed by autophagy agonists and autophagy inhibitors. The expression levels of inflammasome-related protein NLRP3 and autophagy-related proteins LC3B and P62 were detected to test the behavior of rats with a water maze. RESULTS: We found that sevoflurane exposure affected learning and working memory ability in aged rats. ...