Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, China.
Institute of National Security, Minzu University of China, Beijing, China.
J Transl Med. 2023 Apr 3;21(1):241. doi: 10.1186/s12967-023-04070-1.
Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection.
Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects.
Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified.
Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.
远程缺血预处理（RIPC）是指短暂暴露于潜在的不良刺激下，以防止随后暴露时发生损伤。RIPC 已被证明可提高对缺血性损伤的耐受性并改善脑灌注状态。外泌体具有多种活性，如重塑细胞外基质和向其他细胞传递信号。本研究旨在探讨 RIPC 介导的神经保护的潜在分子机制。
将 60 名成年男性军事人员分为对照组（n = 30）和 RIPC 组（n = 30）。我们分析了 RIPC 组和对照组参与者血清外泌体中的差异代谢物和蛋白质。
在 RIPC 组和对照组之间发现了 87 种差异表达的血清外泌体代谢物，这些代谢物富集在与酪氨酸代谢、鞘脂代谢、5-羟色胺能突触和多种神经退行性疾病相关的途径中。此外，在 RIPC 组和对照组之间还发现了 75 种差异表达的外泌体蛋白，这些蛋白涉及胰岛素样生长因子（IGF）转运、嗜中性粒细胞脱颗粒、囊泡介导的运输等调节。此外，我们发现差异表达的可可碱、环甘氨酸、血红素结合蛋白（HPX）和载脂蛋白 A1（ApoA1）与缺血/再灌注损伤中的神经保护益处有关。此外，还鉴定了 5 种潜在的代谢物生物标志物，包括水杨酸乙酯、乙硫异烟胺、胡椒酸、2,6-二叔丁基-4-羟基甲基苯酚和姜烯酮，这些标志物可将 RIPC 与对照组个体区分开来。
我们的数据表明，血清外泌体代谢物是 RIPC 的有前途的生物标志物，我们的结果为进一步分析缺血/再灌注条件下脑缺血再灌注损伤提供了丰富的数据集和框架。
