Xu Fei, Liu Tian-Ping, Guan Ya-Jin, Hao Wei-Chao, Wen Ding-Sheng, Xie Shui-Lin, Bie Ya-Nan
Guangdong Mingzhu Biotechnology Co., Ltd., Foshan 528500, China.
Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510062, China.
Se Pu. 2025 Feb;43(2):139-147. doi: 10.3724/SP.J.1123.2024.02015.
Biomarkers for ischemic stroke (IS) are yet to fulfill clinical requirements. This study used non-targeted metabolomics to investigate differential metabolites and metabolic pathways in plasma and brain tissue following IS, with the aim of identifying new potential biomarkers and therapeutic targets. Twelve Tibetan miniature pigs were randomly assigned to a model- or sham-operation group. An electrocoagulation-based anterior temporal approach was employed to occlude the middle cerebral artery, thereby creating a model for IS. Plasma and brain tissue samples were collected 36 h post-surgery and analyzed using liquid chromatography-mass spectrometry. Principal component and partial least squares discriminant analyses were used to screen for differential metabolites and exclude exogenous metabolites at <0.05. Compounds were classified according to the HMDB (Human Metabolome Database), and subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and VIP (variable importance in projection) analyses. Plasma metabolomics revealed that 86 metabolites were upregulated while 149 were downregulated, with ()-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, -cinnamic acid and cinnamoylglycine determined to be significant metabolites. Fifty-eight differential metabolites were upregulated in brain tissue and 53 were downregulated, with 2,3-dihydroflavon-3-ol, guanidinoacetic acid (GAA), -acetyl-D-tryptophan, oxidized glutathione, 2-hydroxyquinoline, and -acetyl-L-aspartate (NAA) identified as significant metabolites. Organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds, and organic oxygen compounds were found to be common compound categories among the top five types of compound in both plasma and brain tissue. Common metabolic pathways in plasma and brain tissue include amino acid metabolism, digestive system, cancer overview, and lipid metabolism pathways, with the ()-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, GAA, oxidized glutathione, and NAA metabolites serving as potential biomarkers. This study provides a theoretical foundation for the early screening and development of clinical treatment strategies for IS.
缺血性中风（IS）的生物标志物尚未满足临床需求。本研究采用非靶向代谢组学方法，研究IS后血浆和脑组织中的差异代谢物及代谢途径，旨在识别新的潜在生物标志物和治疗靶点。12只西藏小型猪被随机分为模型组或假手术组。采用基于电凝的前颞叶入路闭塞大脑中动脉，从而建立IS模型。术后36小时采集血浆和脑组织样本，并用液相色谱-质谱联用仪进行分析。主成分分析和偏最小二乘判别分析用于筛选差异代谢物，并排除P<0.05的外源性代谢物。根据人类代谢组数据库（HMDB）对化合物进行分类，并进行京都基因与基因组百科全书（KEGG）通路和投影变量重要性（VIP）分析。血浆代谢组学显示，86种代谢物上调，149种代谢物下调，其中（）-3-氧代-2-（2-戊烯基）-1-环戊基乙酸、反式肉桂酸和肉桂酰甘氨酸被确定为显著代谢物。脑组织中有58种差异代谢物上调，53种差异代谢物下调，其中2,3-二氢黄酮-3-醇、胍基乙酸（GAA）、N-乙酰-D-色氨酸、氧化型谷胱甘肽、2-羟基喹啉和N-乙酰-L-天冬氨酸（NAA）被确定为显著代谢物。有机酸及其衍生物、脂质和类脂分子、有机杂环化合物以及有机氧化合物是血浆和脑组织中排名前五的化合物类型中常见的化合物类别。血浆和脑组织中的共同代谢途径包括氨基酸代谢、消化系统、癌症概述和脂质代谢途径，其中（）-3-氧代-2-（2-戊烯基）-1-环戊基乙酸、GAA、氧化型谷胱甘肽和NAA代谢物可作为潜在生物标志物。本研究为IS临床治疗策略的早期筛选和开发提供了理论基础。
