Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
J Proteomics. 2021 May 30;240:104190. doi: 10.1016/j.jprot.2021.104190. Epub 2021 Mar 23.
Chronic stressors represented risk factors for the etiology or exacerbation of several gastrointestinal diseases. The goal of the present study was to examine whether chronic restraint stress (CRS) could initiate and aggravate colonic inflammation, integrity damage and metabolic disturbance of rats. Firstly, increased inflammatory cytokines (interferon-γ (IFN-γ), tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10)) and decreased tight junction (TJ) proteins (occludin and zonula occludins-1 (ZO-1)) in rat colon were observed. Secondly, untargeted metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass (UPLC-Q-TOF/MS) revealed that TRP metabolism was the most prominently affected. Thirdly, quantification of TRP and its metabolites via prominence ultrafast liquid chromatography coupled with a QTRAP 5500 mass (UFLC-QTRAP-5500/MS) showed that TRP, kynurenine (KYN), kynurenic acid (KA) and 3-hydroxykynurenine (3-HK) were significantly increased. At the same time, 5-hydroxytryptamine (5-HT) was unchanged and 5-hydroxyindolacetic acid (5-HIAA) was significantly decreased in the colon of CRS rats. Besides, TRP metabolic enzyme changes were with the same trends as the corresponding metabolites. Thus, our data showed that CRS could initiate colonic inflammation, integrity damage and colonic metabolism disturbance, especially TRP-KYN metabolism pathway of rats, which may provide an experimental background for future research on stress-related gastrointestinal dysfunction. SIGNIFICANCE: Chronic exposure to psychological stress could induce metabolic imbalance of the body, and stressful life events were intimately correlated with frequent relapses in patients with intestinal disorders. The present study showed that chronic restraint stress (CRS) could initiate and aggravate colonic inflammation, integrity damage and metabolic disturbance, especially tryptophan-kynurenine metabolism of rats. Tryptophan-kynurenine pathway may be involved in the initiation and development of diseases induced by chronic stress. This research may shed light on future research on stress-related gastrointestinal dysfunction.
慢性应激源代表了几种胃肠道疾病的病因或恶化的危险因素。本研究的目的是研究慢性束缚应激（CRS）是否会引发和加重大鼠结肠炎症、完整性损伤和代谢紊乱。首先，观察到大鼠结肠中炎症细胞因子（干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10））增加和紧密连接（TJ）蛋白（闭合蛋白和闭锁蛋白-1（ZO-1））减少。其次，基于超高效液相色谱与四极杆飞行时间质谱（UPLC-Q-TOF/MS）的非靶向代谢组学显示，TRP 代谢受到的影响最为显著。第三，通过突显快速液相色谱与 QTRAP 5500 质谱联用（UFLC-QTRAP-5500/MS）对 TRP 及其代谢物进行定量，发现 TRP、犬尿氨酸（KYN）、犬尿喹啉酸（KA）和 3-羟基犬尿氨酸（3-HK）明显增加。同时，CRS 大鼠结肠中 5-羟色胺（5-HT）不变，5-羟吲哚乙酸（5-HIAA）明显减少。此外，TRP 代谢酶的变化与相应代谢物的变化趋势相同。因此，我们的数据表明，CRS 可引发结肠炎症、完整性损伤和结肠代谢紊乱，特别是大鼠的 TRP-KYN 代谢途径，这可能为未来研究应激相关的胃肠道功能障碍提供实验背景。意义：慢性暴露于心理应激可导致机体代谢失衡，应激性生活事件与肠道疾病患者的频繁复发密切相关。本研究表明，慢性束缚应激（CRS）可引发和加重大鼠结肠炎症、完整性损伤和代谢紊乱，特别是大鼠的色氨酸-犬尿氨酸代谢。色氨酸-犬尿氨酸途径可能参与了慢性应激诱导的疾病的发生和发展。这项研究可能为未来研究应激相关的胃肠道功能障碍提供启示。
