单位：[1]Department of Anesthesiology,Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health,and Wuhan Clinical Research Center for Geriatric Anesthesia,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,People’s Republic of China麻醉科华中科技大学同济医学院附属同济医院综合医疗科
Postoperative neurocognitive dysfunction (PND) is a common postoperative complication. Autophagy is correlated with the pathogenesis of PND. This study investigated the potential role of autophagy in the neuroprotection of dexmedetomidine (Dex) pretreatment in PND. The PND rat model was established by abdominal surgery. The cognitive function of rats was evaluated by Y-maze 3 days after surgery. Nissl staining assessed postoperative hippocampal damage. Immunofluorescence detected the expression of microglial activation (Iba-1) and autophagy-related protein (LC3B) in hippocampal tissues. Western blot detected the autophagy-related protein expression (Beclin 1, LC3B, and p62), proinflammatory cytokines, and the protein activation of the autophagy-related LKB1/AMPK/ULK-1 signaling pathway. RT-PCR quantified the expression of IL-1β, TNF-α, and IL6. In this study, we found that Dex pretreatment improved spatial memory function impairment and reduced abdominal surgery-induced hippocampal tissue damage. Dex pretreatment significantly increased the expression of Beclin 1 and LC3 II/I and decreased the expression of p62 in the hippocampus after surgery. Furthermore, Dex effectively inhibited microglial activation and proinflammatory cytokines by enhancing autophagy in the hippocampus. Pretreatment with 3-MA, an autophagy inhibitor, significantly weakened the inhibitory effect of Dex on postoperative neuroinflammation. We further demonstrated that Dex suppressed surgery-induced neuroinflammation by activating the LKB1/AMPK/ULK-1 signaling pathway. In conclusion, our study indicated that Dex inhibited hippocampal neuroinflammation and ameliorated PND by enhancing autophagy after surgery in rats, which was related to the LKB1/AMPK/ULK-1 signaling pathway. These findings provide a potential therapeutic prospect for PND.NEW & NOTEWORTHY Dex inhibits hippocampal neuroinflammation and attenuates early cognitive impairment by enhancing autophagy following surgery in rats. Dex may protect postoperative cognitive function by activating the LKB1/AMPK/ULK-1 signaling pathway.
基金：
This work was supported by the Natural Science Foundation of
Hubei Province under Grant No. 2021CFB374.
第一作者单位：[1]Department of Anesthesiology,Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health,and Wuhan Clinical Research Center for Geriatric Anesthesia,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,People’s Republic of China
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Jinxu,Xin Yueyang,Chu Tiantian,et al.Dexmedetomidine mitigates neuroinflammation and improves early postoperative neurocognitive dysfunction in rats by enhancing autophagy[J].JOURNAL OF NEUROPHYSIOLOGY.2023,129(5):1145-1156.doi:10.1152/jn.00019.2023.
APA：
Wang Jinxu,Xin Yueyang,Chu Tiantian,Zhou Yaqun,Liu Cheng&Xu Aijun.(2023).Dexmedetomidine mitigates neuroinflammation and improves early postoperative neurocognitive dysfunction in rats by enhancing autophagy.JOURNAL OF NEUROPHYSIOLOGY,129,(5)
MLA：
Wang Jinxu,et al."Dexmedetomidine mitigates neuroinflammation and improves early postoperative neurocognitive dysfunction in rats by enhancing autophagy".JOURNAL OF NEUROPHYSIOLOGY 129..5(2023):1145-1156
