Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.
Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.
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老年髋部骨折术后谵妄患者术前脑脊液的代谢组学和脂质组学分析
DOI：
10.3389/fnagi.2020.570210
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发表时间：
2020
影响因子：
4.8
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Han Y;Zhang W;Liu J;Song Y;Liu T;Li Z;Wang X;Yang N;Li Y;Han D;Mi X;Zhou Y;Li M;Guo X;Zhong L;Wang G;Yuan Y
目的探讨老年髋部骨折术后谵妄（POD）患者术前脑脊液（CSF）中的异常分子，探讨早期谵妄的潜在病理机制和生物标志物。材料和方法：本巢式病例对照研究采用非靶向代谢组学和脂质组学分析，对发生POD的患者（n = 40）进行髋部骨折手术（n = 10）和未发生POD的患者（n = 30）进行术前脑脊液分析。30例非POD患者与10例POD患者按年龄（±2岁）和迷你精神状态检查评分（±2分）进行配对。脊髓麻醉成功后采集脑脊液，保存以供后续分析。术后前两天，使用混淆评估法-中文修订版每日对患者进行两次评估。对两组脑脊液样本进行分析，以探讨可能的相关病理机制并确定候选生物标志物。结果两组人口统计学特征吻合。POD患者术前脑脊液中有18种代谢物和33种脂质异常。途径富集分析揭示了d -谷氨酰胺和d -谷氨酸代谢的扰动；glycerophospholipid新陈代谢;丙氨酸、天冬氨酸和谷氨酸代谢；鞘脂类代谢;组氨酸代谢;以及谵妄前期的精氨酸生物合成。受试者工作特征曲线分析表明，磷脂酰乙醇胺（PE, 40:7e）是POD的潜在生物标志物，曲线下面积为0.92。结论POD组患者术前的病理机制涉及多种，包括缺氧引起的神经炎症、氧化应激、能量代谢紊乱，以及多巴胺、谷氨酸升高、谷氨酰胺降低等神经递质失衡。这些代谢异常可能会增加大脑的脆弱性，从而导致POD。PE （40:7e）可能是POD的潜在生物标志物。我们的结果不仅为POD提供了潜在的生物标志物，也为深入的病理研究提供了信息。临床试验注册www.ClinicalTrials.gov，标识符ChiCTR1900021533。
Objective To investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD. Materials and Methods This nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (n = 40) who developed POD undergone hip fracture surgery (n = 10) and those who did not (n = 30). Thirty Non-POD patients were matched to 10 POD patients by age (± 2 years) and Mini Mental State Examination score (± 2 points). CSF was collected after successful spinal anesthesia and banked for subsequent analysis. On the first two postoperative days, patients were assessed twice daily using the Confusion Assessment Method-Chinese Revision. CSF samples from the two groups were analyzed to investigate possible relevant pathological mechanisms and identify candidate biomarkers. Results Demographic characteristics of the groups were matched. Eighteen metabolites and thirty-three lipids were dysregulated in the preoperative CSF of POD patients. Pathway enrichment analysis revealed perturbations in D-glutamine and D-glutamate metabolism; glycerophospholipid metabolism; alanine, aspartate and glutamate metabolism; sphingolipid metabolism; histidine metabolism; and arginine biosynthesis at the pre-delirium stage. Receiver operating characteristic curve analysis indicated that phosphatidylethanolamine (PE, 40:7e), with an area under the curve value of 0.92, is a potential biomarker for POD. Conclusion Multiple pathological mechanisms in the POD group were involved before surgery, including neuroinflammation, oxidative stress, and energy metabolism disorders induced by hypoxia, as well as neurotransmitter imbalances such as increased dopamine and glutamate, and decreased glutamine. These metabolic abnormalities potentially increase the fragility of the brain, thus contributing to POD. PE (40:7e) might be a potential biomarker for POD. Not only do our results provide potential biomarkers for POD, but also provide information for deep pathological research. Clinical Trial Registration www.ClinicalTrials.gov, identifier ChiCTR1900021533.
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影响因子：
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