Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
Clin Nutr. 2024 Sep;43(9):2198-2210. doi: 10.1016/j.clnu.2024.07.039. Epub 2024 Aug 12.
Perioperative neurocognitive dysfunction (PND) occurs in elderly individuals undergoing anesthesia and surgery. To explore the potential molecular mechanisms, we performed right-sided cervical exploratory surgery under sevoflurane anesthesia in 18-month-old male Sprague-Dawley rats. Anxiety-depression-like behaviors and learning memory abilities were assessed using the Open Field Test (OFT) and Novel Object Recognition (NOR). Additionally, the hippocampus was collected one day after surgery for inflammatory factor detection, TUNEL staining, and metabolomics analysis. Mendelian randomization (MR) analyses were subsequently conducted to validate the causal relationships by using a series of GWAS datasets related to representative differential metabolites as exposures and cognitive impairment as endpoints. The results indicated that rats exposed to anesthesia and surgery exhibited poorer cognitive performance, significant elevations in hippocampal inflammatory factors such as IL-1β and TNF-α, and extensive neuronal apoptosis. LC-MS/MS-based untargeted metabolomics identified 19 up-regulated and 32 down-regulated metabolites in the test group, with 6 differential metabolites involved in metabolic pathways enriched according to the KEGG database. ROC analysis revealed a correlation between α-linolenic acid (ALA) and linoleic acid (LA) and the development of PND. Further MR analysis confirmed that ALA was significantly associated with cognitive performance and the risk of depression, while LA was significantly associated with the risk of memory loss. Taken together, our results identified ALA and LA as potentially powerful biomarkers for PND.
围手术期神经认知功能障碍（PND）发生在接受麻醉和手术的老年患者中。为了探索潜在的分子机制，我们在 18 个月大的雄性 Sprague-Dawley 大鼠中进行了右颈探查手术，使用七氟醚麻醉。使用旷场试验（OFT）和新物体识别（NOR）评估焦虑抑郁样行为和学习记忆能力。术后一天收集海马组织，用于炎症因子检测、TUNEL 染色和代谢组学分析。随后进行孟德尔随机化（MR）分析，使用与代表性差异代谢物相关的一系列 GWAS 数据集作为暴露因素，以认知障碍作为终点，验证因果关系。结果表明，暴露于麻醉和手术的大鼠表现出较差的认知表现，海马炎症因子如 IL-1β 和 TNF-α显著升高，神经元凋亡广泛。基于 LC-MS/MS 的非靶向代谢组学鉴定出实验组中有 19 个上调和 32 个下调的代谢物，根据 KEGG 数据库，有 6 个差异代谢物参与代谢途径富集。ROC 分析显示，α-亚麻酸（ALA）和亚油酸（LA）与 PND 的发生呈正相关。进一步的 MR 分析证实，ALA 与认知表现和抑郁风险显著相关，而 LA 与记忆丧失风险显著相关。总之，我们的研究结果确定了 ALA 和 LA 可能是 PND 的潜在有力生物标志物。
