Chen Qiong, Zhou Ting, Yuan Jun-Jie, Xiong Xiao-Yi, Liu Xue-Hui, Qiu Zong-Ming, Hu Lin-Lin, Lu Hui, He Qian, Liu Chang, Yang Qing-Wu
Department of Neurology, Xinqiao Hospital, The Army Medical University (Third Military Medical University), Chongqing, China.
Sichuan Provincial Key Laboratory for Acupuncture & Chronobiology, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2023 Feb 6;14:1091616. doi: 10.3389/fphar.2023.1091616. eCollection 2023.
Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.
脑缺血是全球主要死因之一，由血流受损引起，治疗选择有限。再灌注治疗导致的潜在有害损伤仍是医生面临的临床挑战。本研究旨在通过气相色谱飞行时间质谱（GC-TOF-MS）和超高效液相色谱四极杆（UPLC/Q）-TOF-MS联用的代谢组学分析方法，探索缺血再灌注损伤期间的代谢组学变化。将大脑中动脉闭塞（MCAO）后再灌注（MCAO/R）小鼠的代谢组学数据与假手术组和MCAO组进行比较。每组共鉴定出82种同时差异表达的代谢物。这些差异表达代谢物的前三大主要分类是有机酸、脂质和有机氧化合物。进行代谢组学通路分析以确定与MCAO/R相关的潜在通路。根据影响因子得分，脑缺血后再灌注反应中最显著的通路是甘油磷脂代谢、亚油酸代谢、嘧啶代谢和半乳糖代谢。与假手术组和MCAO组相比，这82种代谢物中有17种在MCAO/再灌注组中显著升高。在这些代谢物中，与MCAO组相比，6-磷酸葡萄糖1、6-磷酸果糖、纤维二糖2、O-膦酰苏氨酸1和水杨苷是MCAO/R组中升高的前五种代谢物。根据代谢物集富集分析（MSEA），糖酵解、磷酸戊糖途径、淀粉和蔗糖代谢以及果糖和甘露糖降解是排名前四的通路。本研究不仅增进了我们对假手术组和脑缺血组动物在有或无再灌注代谢组学分析情况下代谢组学变化的理解，还为探索脑缺血再灌注诱导的代谢改变的潜在分子机制铺平了道路。
