Exposure to repeated stress is associated with the occurrence and development of many prevalent diseases. Here, we evaluated the impact of a repeated restraint stress (RRS) paradigm on male Wistar rats and compared global plasma metabolites in stressed and unstressed rats using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) approach and multivariate statistical analysis. The data showed that ten days of RRS induced weight loss and anxiety-like behavior, possibly through elevating plasma corticosterone levels in rats. Different metabolic characteristics were found between the two groups. Seventeen differential metabolites were identified and considered as potential biomarkers in the stress process, including histidine metabolism, neurotransmitter synthesis, and bile acid metabolism. Furthermore, l-carnosine, an identified metabolite, was examined in the same model and found to attenuate weight loss and anxiety-like behavior in RRS rats. Hence, these findings describe the metabolomic profiling of repeated stress and provide new insights into the pathophysiological mechanism of stress-induced deflections and potential pharmacological interventions.

反复承受压力与许多流行疾病的发生和发展有关。在这里，我们评估了重复约束压力（RRS）范式对雄性Wistar大鼠的影响，并使用超高效液相色谱-四极杆飞行时间质谱（UHPLC / Q）比较了应激和无应激大鼠的整体血浆代谢物-TOF-MS）方法和多元统计分析。数据显示，十天的RRS可能导致大鼠血浆皮质酮水平升高，从而引起体重减轻和焦虑样行为。两组之间发现了不同的代谢特征。确定了十七种差异代谢物，并将其视为应激过程中的潜在生物标志物，包括组氨酸代谢，神经递质合成和胆汁酸代谢。升-carnosine，识别的代谢产物，在同一个模型了检查，发现衰减减肥和焦虑样的RRS大鼠的行为。因此，这些发现描述了重复应激的代谢组学谱，并为应激诱发的偏斜的病理生理机制和潜在的药理学干预提供了新的见识。