非靶向代谢组学揭示癫痫大鼠心肌代谢改变
Non-targeted metabolomics reveals myocardial metabolic alterations in epileptic rats.
摘要(中文译文)
癫痫猝死（SUDEP）与心血管功能障碍密切相关，但其机制尚不清楚。新出现的证据提示，癫痫所致心脏功能障碍可能发挥核心作用。代谢组学为全面表征这些代谢改变提供了有力手段，有助于发现生物标志物并深入理解癫痫相关心脏损伤的机制。本研究采用基于UHPLC-OE-MS的非靶向代谢组学方法，系统表征癫痫大鼠的心肌代谢，旨在识别癫痫相关心肌代谢生物标志物，探讨其生物学意义，并阐明癫痫所致心脏功能障碍的机制。在本研究中，我们采用基于UHPLC-OE-MS的非靶向代谢组学方法，系统分析了戊四氮（PTZ）诱导的癫痫大鼠模型中心肌代谢变化。采用多元统计方法，包括主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），对癫痫组和对照组大鼠的心肌组织进行分析，以识别显著改变的代谢物。通过KEGG通路富集分析阐明这些代谢紊乱的生物学相关性。组织病理学检查显示，癫痫大鼠存在明显的神经元排列紊乱和心肌损伤，表现为心肌细胞肿胀、核固缩和间质水肿。代谢组学分析鉴定出127种差异代谢物，主要涉及氨基酸代谢、甘油磷脂代谢和能量代谢。值得注意的是，L-谷氨酰胺、L-苯丙氨酸、L-丙氨酸和β-丙氨酸显著降低，可能促进谷氨酸/GABA失衡、兴奋性毒性和氧化应激。此外，甘油磷脂（如LysoPC、PC和PE）失调以及泛酸和CoA生物合成改变，提示癫痫心肌膜完整性受损和能量代谢障碍。ROC分析显示关键代谢物具有优异的诊断效能（AUC > 0.98），凸显其作为癫痫相关心脏功能障碍生物标志物的潜力。
Abstract
Sudden unexpected death in epilepsy (SUDEP) is closely associated with cardiovascular dysfunction, yet its mechanisms remain unclear. Emerging evidence suggests that epilepsy-induced cardiac dysfunction may play a central role. Metabolomics provides a powerful approach to comprehensively characterize these metabolic alterations, enabling biomarker discovery and mechanistic insight into epilepsy-related cardiac injury. Here, we used UHPLC-OE-MS-based non-targeted metabolomics to systematically characterize myocardial metabolism in epileptic rats, aiming to identify epilepsy-related myocardial metabolic biomarkers, explore their biological significance, and elucidate mechanisms underlying epilepsy-induced cardiac dysfunction. In this study, we employed UHPLC-OE-MS-based non-targeted metabolomics to systematically profile myocardial metabolic changes in a pentylenetetrazol (PTZ)-induced epileptic rat model. Myocardial tissues from epileptic and control rats were analyzed using multivariate statistical methods, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to identify significantly altered metabolites. KEGG pathway enrichment analysis was performed to elucidate the biological relevance of these metabolic disturbances. Histopathological examination revealed marked neuronal disorganization and myocardial injury in epileptic rats, characterized by cardiomyocyte swelling, nuclear pyknosis, and interstitial edema. Metabolomic analysis identified 127 differential metabolites, primarily involved in amino acid metabolism, glycerophospholipid metabolism, and energy metabolism. Notably, L-glutamine, L-phenylalanine, L-alanine, and β-alanine were significantly reduced, potentially contributing to glutamate/GABA imbalance, excitotoxicity, and oxidative stress. Additionally, dysregulated glycerophospholipids (e.g., LysoPC, PC, and PE) and altered pantothenate and CoA biosynthesis indicated compromised membrane integrity and impaired energy metabolism in epileptic myocardium. ROC analysis demonstrated excellent diagnostic performance of key metabolites (AUC > 0.98), highlighting their potential as biomarkers for epilepsy-related cardiac dysfunction.
如何引用
AMA
Yue Hu, Yusen Wang, Qinghong Mao, Shisheng Zhu, Li Zhang. Non-targeted metabolomics reveals myocardial metabolic alterations in epileptic rats.. PloS one. 2026; doi:10.1371/journal.pone.0346628.
APA
Yue Hu, Yusen Wang, Qinghong Mao, Shisheng Zhu, Li Zhang (2026). Non-targeted metabolomics reveals myocardial metabolic alterations in epileptic rats.. PloS one. https://doi.org/10.1371/journal.pone.0346628
GB/T 7714
Yue Hu, Yusen Wang, Qinghong Mao, Shisheng Zhu, Li Zhang. Non-targeted metabolomics reveals myocardial metabolic alterations in epileptic rats.[J]. PloS one, 2026 doi:10.1371/journal.pone.0346628.
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