摘要
多发性硬化(multiple sclerosis,MuS)是一种中枢神经系统慢性炎症和脱髓鞘疾病,全球患病率持续上升。其发病机制复杂,涉及免疫异常、遗传及环境因素,临床表现多样,在诊断与治疗方面面临挑战。代谢组学通过分析小分子代谢物,为揭示MuS病理机制和识别生物标志物开辟了新途径,尤其是在氨基酸和脂质代谢异常与炎症、髓鞘损伤及免疫反应关联的研究中发挥着重要作用。本文综述了色谱-质谱技术在MuS代谢标志物研究中的应用进展,聚焦氨基酸和脂质代谢的关键作用。回顾了液相色谱-串联质谱、高分辨质谱、气相色谱-质谱及基质辅助激光解吸电离-飞行时间质谱等技术,分析了MuS患者体液和组织样本中的代谢变化。通过总结代表性研究,探讨了这些技术在代谢物检测方面的应用。结果显示,MuS患者脑脊液中精氨酸代谢和色氨酸代谢途径紊乱,与氧化应激相关的焦谷氨酸水平发生变化;脂质代谢方面,脂肪酸、胆固醇和鞘脂代谢异常与免疫失调、髓鞘损伤及神经炎症关联。色谱-质谱技术以高灵敏度、高分辨率和高通量优势,为揭示MuS代谢异常发挥关键作用,为早期诊断、病情监测及个性化治疗提供了潜在标志物。
Multiple sclerosis(MuS)is a chronic,inflammatory,demyelinating disease of the central nervous system,with a globally increasing prevalence.Its pathogenesis involves complex interactions among immune dysregulation,genetic predisposition,and environmental factors.These contribute to a wide spectrum of clinical manifestations,posing significant challenges for both diagnosis and treatment.Metabolomics,the comprehensive analysis of small-molecule metabolites,has emerged as a powerful approach to elucidate MuS pathophysiology and identify potential biomarkers.In particular,alterations in amino acid and lipid metabolism are closely associated with inflammation,myelin damage,neurotransmitter imbalance,and immune activation.This review summarizes recent advancements in the application of chromatography-mass spectrometry techniques to MuS biomarker research.Key technologies include liquid chromatography-tandem mass spectrometry(LC-MS/MS)for analyzing metabolites in biological fluids,high resolution mass spectrometry(HRMS)for precise metabolite identification,gas chromatography-mass spectrometry(GC-MS)for profiling volatile compounds,and matrix-assisted laser desorption ionization-time of flight mass spectrometry(MALDITOF MS)for mapping spatial metabolite distributions in tissues.Metabolomic analyses of MuS patient samples have revealed significant disruptions in amino acid metabolism.For instance,reduced arginine levels and elevated asymmetric dimethylarginine levels in cerebrospinal fluid suggest vascular dysfunction.Altered tryptophan metabolism,including altered levels of kynurenic acid and 5-hydroxytryptophan,reflects neurotransmitter imbalances.Increased pyroglutamic acid levels indicate oxidative stress.Lipid metabolism is also markedly perturbed in MuS.Changes in palmitic acid levels affect cell membrane integrity,while alterations in sphingolipids,key components of myelin,are linked to demyelination.Elevated oxysterols correlate with neuroinflammation and immune dysregulation.Additionally,systemic lipid changes,such as reduced low-density lipoprotein and altered high-density lipoprotein cholesterol levels,have been associated with disease activity and progression.Due to their high sensitivity,resolution,and throughput,chromatography-mass spectrometry techniques are well-suited for detecting these metabolic alterations.Representative studies demonstrate the utility of LC-MS/MS in detecting amino acid perturbations in plasma and cerebrospinal fluid(CSF),GC-MS in identifying lipid abnormalities in serum,HRMS in generating detailed brain tissue metabolite profiles,and MALDI-TOF MS in visualizing lesion-specific metabolic distributions.These findings have led to the identification of promising biomarker candidates.For instance,decreased arginine may indicate endothelial dysfunction,while elevated oxysterols may serve as markers of neuroinflammatory activity.Such biomarkers hold potential for facilitating early diagnosis,disease monitoring,and personalized treatment strategies.Metabolomics via chromatography-mass spectrometry technologies has significantly advanced our understanding of MuS pathophysiology.Amino acid dysregulation affects neurotransmitter synthesis and immune modulation,while lipid imbalances impair myelin integrity and cellular signaling.These insights provide a foundation for the development of metabolite-based diagnostic tools and therapeutic interventions.Nonetheless,several challenges remain.MuS exhibits high heterogeneity,and metabolomic data are complex and variable.Improved biomarker specificity and standardization are needed for clinical application.Technological advances in chromatography-mass spectrometry resolution,along with standardized protocols,will be essential.Large-scale clinical validation across MuS subtypes is also critical.Integrating metabolomics with genomics and environmental factors may enhance biomarker reliability and elucidate individual disease trajectories.In conclusion,this review highlights the crucial role of chromatography-mass spectrometry-based metabolomics in MuS research.By unraveling the metabolic underpinnings of inflammation and demyelination,it provides valuable insights into disease mechanisms and introduces novel avenues for early diagnosis and targeted therapy.Collaborative research efforts and methodological rigor will be key to translating these discoveries into clinical impact.
作者
要振榆
王玉飞
朱晓雯
杨红
武佳
张国军
YAO Zhenyu;WANG Yufei;ZHU Xiaowen;YANG Hong;WU Jia;ZHANG Guojun(Laboratory Diagnosis Center,Beijing Tiantan Hospital,Capital Medical University,NMPA Key Laboratory for Quality Control for In Vitro Diagnostic,National Engineering Research Centre for Beijing Biochip Technology,Laboratory Diagnosis Platform for Nervous System Infectious Diseases,Laboratory for Clinical Medicine,Capital Medical University,Beijing 100070,China;Yanjing Medical College,Capital Medical University,Beijing 101300,China)
出处
《色谱》
北大核心
2026年第3期226-233,共8页
Chinese Journal of Chromatography
基金
国家自然科学基金(82002198)
首都医科大学燕京医学院科研培育基金(22jl01)。
关键词
多发性硬化
色谱-质谱
生物标志物
氨基酸代谢
脂质代谢
multiple sclerosis(MuS)
chromatography-mass spectrometry
biomarkers
amino acid metabolism
lipid metabolism
