Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice.
Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice.
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代谢组学分析表征小鼠脑缺血再灌注损伤。
DOI：
10.3389/fphar.2023.1091616
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
由血流受损引起的脑缺血是全世界死亡的主要原因之一，治疗选择有限。再灌注治疗造成的潜在有害损伤仍然是医生面临的临床挑战。本研究旨在通过采用代谢组学分析结合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来探讨缺血再灌注损伤期间的代谢组变化。将大脑中动脉闭塞 (MCAO) 再灌注 (MCAO/R) 小鼠的代谢组数据与假手术组和 MCAO 组的代谢组数据进行比较。每组中总共鉴定出 82 个同时差异表达的代谢物。这些差异表达代谢物的前三大类是有机酸、脂质和有机氧化合物。进行代谢组学途径分析以确定 MCAO/R 涉及的潜在途径。根据撞击评分，参与脑缺血后再灌注反应的最重要途径是甘油磷脂代谢、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，MCAO/再灌注组的 82 种代谢物中有 17 种显着升高。其中，与 MCAO 组相比，MCAO/R 组升高的前 5 种代谢物为葡萄糖-6-磷酸 1、果糖-6-磷酸、纤维二糖 2、邻磷酸苏氨酸 1 和水杨苷。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途径。本研究不仅通过代谢组学分析加深了我们对假手术组和脑缺血组动物代谢组变化的理解，而且还为探索脑缺血再灌注引起的代谢改变的潜在分子机制铺平了道路。
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 via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.
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DOI：
10.33696/immunology.3.123
发表时间：
2021
期刊：
Journal of cellular immunology
影响因子：
--
作者：
Hammond TC;Xing X;Yanckello LM;Stromberg A;Chang YH;Nelson PT;Lin AL
通讯作者：
Lin AL
影响因子：
4.8
作者：
Ghosh, A;Cheung, YY;Chou, JY
通讯作者：
Chou, JY
影响因子：
6.3
作者：
Diaz, Francisca;Raval, Ami P.
通讯作者：
Raval, Ami P.
DOI：
10.1073/pnas.0902640106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Kolstoe, Simon E.;Ridha, Basil H.;Pepys, Mark B.
通讯作者：
Pepys, Mark B.
影响因子：
16.6
作者：
Ding J;Ji J;Rabow Z;Shen T;Folz J;Brydges CR;Fan S;Lu X;Mehta S;Showalter MR;Zhang Y;Araiza R;Bower LR;Lloyd KCK;Fiehn O
通讯作者：
Fiehn O