Huang Dunbing, Yang Yihan, Song Wei, Jiang Cai, Zhang Yuhao, Zhang Anren, Lin Zhonghua, Ke Xiaohua
Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Front Neurosci. 2023 Aug 8;17:1084813. doi: 10.3389/fnins.2023.1084813. eCollection 2023.
Brain tissue damage caused by ischemic stroke can trigger changes in the body's metabolic response, and understanding the changes in the metabolic response of the gut after stroke can contribute to research on poststroke brain function recovery. Despite the increase in international research on poststroke metabolic mechanisms and the availability of powerful research tools in recent years, there is still an urgent need for poststroke metabolic studies. Metabolomic examination of feces from a cerebral ischemia-reperfusion rat model can provide new insights into poststroke metabolism and identify key metabolic pathways, which will help reveal diagnostic and therapeutic targets as well as inspire pathophysiological studies after stroke.
We randomly divided 16 healthy adult pathogen-free male Sprague-Dawley (SD) rats into the normal group and the study group, which received middle cerebral artery occlusion/reperfusion (MCAO/R). Ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMS/MS) was used to determine the identities and concentrations of metabolites across all groups, and filtered high-quality data were analyzed for differential screening and differential metabolite functional analysis.
After 1 and 14 days of modeling, compared to the normal group, rats in the study group showed significant neurological deficits ( < 0.001) and significantly increased infarct volume (day 1: < 0.001; day 14: = 0.001). Mass spectra identified 1,044 and 635 differential metabolites in rat feces in positive and negative ion modes, respectively, which differed significantly between the normal and study groups. The metabolites with increased levels identified in the study group were involved in tryptophan metabolism ( = 0.036678, < 0.05), arachidonic acid metabolism ( = 0.15695), cysteine and methionine metabolism ( = 0.24705), and pyrimidine metabolism ( = 0.3413), whereas the metabolites with decreased levels were involved in arginine and proline metabolism ( = 0.15695) and starch and sucrose metabolism ( = 0.52256).
We determined that UPLC-MS/MS could be employed for untargeted metabolomics research. Moreover, tryptophan metabolic pathways may have been disordered in the study group. Alterations in the tryptophan metabolome may provide additional theoretical and data support for elucidating stroke pathogenesis and selecting pathways for intervention.
缺血性中风引起的脑组织损伤可引发机体代谢反应的变化，了解中风后肠道代谢反应的变化有助于中风后脑功能恢复的研究。尽管近年来国际上对中风后代谢机制的研究有所增加，且有强大的研究工具可用，但中风后代谢研究仍迫切需要。对脑缺血再灌注大鼠模型粪便进行代谢组学检测可为中风后代谢提供新见解，识别关键代谢途径，这将有助于揭示诊断和治疗靶点，并启发中风后的病理生理学研究。
我们将16只健康成年无特定病原体雄性Sprague-Dawley（SD）大鼠随机分为正常组和研究组，研究组接受大脑中动脉闭塞/再灌注（MCAO/R）。采用超高效液相色谱-串联质谱（UPLC-MS/MS）测定所有组代谢物的种类和浓度，并对过滤后的高质量数据进行差异筛选和差异代谢物功能分析。
建模1天和14天后，与正常组相比，研究组大鼠出现明显的神经功能缺损（<0.001），梗死体积显著增加（第1天：<0.001；第14天：=0.001）。质谱分析分别在正离子和负离子模式下鉴定出大鼠粪便中1044种和635种差异代谢物，正常组和研究组之间差异显著。研究组中水平升高的代谢物参与色氨酸代谢（=0.036678，<0.05）、花生四烯酸代谢（=0.15695）、半胱氨酸和甲硫氨酸代谢（=0.24705）以及嘧啶代谢（=0.3413），而水平降低的代谢物参与精氨酸和脯氨酸代谢（=0.15695）以及淀粉和蔗糖代谢（=0.52256）。
我们确定UPLC-MS/MS可用于非靶向代谢组学研究。此外，研究组色氨酸代谢途径可能已紊乱。色氨酸代谢组的改变可能为阐明中风发病机制和选择干预途径提供额外的理论和数据支持。
