In vivo redox imaging of dextran sodium sulfate-induced colitis in mice using Overhauser-enhanced magnetic resonance imaging
In vivo redox imaging of dextran sodium sulfate-induced colitis in mice using Overhauser-enhanced magnetic resonance imaging
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DOI：
10.1016/j.freeradbiomed.2019.03.025
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发表时间：
2019-05-20
影响因子：
7.4
通讯作者：
Utsumi, Hideo
中科院分区：
文献类型：
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作者：
Yasukawa, Keiji;Hirago, Akinobu;Utsumi, Hideo
溃疡性结肠炎是一种原因不明的炎症性肠病，需要在早期诊断结肠炎的程度和部位，以控制症状。氧化还原状态的变化，包括活性氧和氮物质（RONS）的产生，与人类溃疡性结肠炎和啮齿动物葡聚糖硫酸钠（DSS）诱导的结肠炎有关。在这项研究中，在DSS诱导的结肠炎小鼠结肠的体内氧化还原状态的Overhauser增强磁共振成像（OMRI）监测，并探讨氧化还原状态与结肠炎的发展之间的关系。通过向雄性Slc：ICR小鼠施用在饮用水中的5%DSS来诱导结肠炎，所述小鼠是分类为封闭群远系杂交小鼠的品系（5周龄，25-30 g）。在DSS激发的第3天，当未显示结肠炎症状时，N-15-CmP和N-14-CxP的对比度衰减倾向于显示整个结肠中的增强，并且未被DMSO改变。在DSS激发的第5天，显示直肠的组织学损伤，N-15-CmP的对比度衰减不仅在直肠中，而且在近端结肠中显著增强，并且这被DMSO抑制。在DSS攻击的第7天，小鼠表现出严重的结肠炎症状，N-15-标记的3-氨基甲酰基-2，2，5，5-四甲基吡咯烷-1-氧基的图像对比（N-15-CmP）和N-14-标记的3-羧基-2，2，5，5-四甲基吡咯烷-1-氧基（N-14-CxP）的衰变速度比健康小鼠快得多，而两种探针增加的衰变可通过膜渗透性活性氧（ROS）清除剂二甲基亚砜（DMSO）恢复。N-15-CmP和N-14-CxP的衰减速率图像之间的图像差异显示DSS诱导的氧化还原失衡遍布整个结肠，并且差异图像的直方图显示DSS处理的峰较小且分布较广。这些数据表明，在DSS诱导的结肠炎的起始阶段，ROS在远端和近端结肠中细胞内产生，并且在DSS诱导的结肠炎的晚期阶段，ROS在细胞内和细胞外产生。
In ulcerative colitis, an inflammatory bowel disease of unknown cause, diagnosis of the degree and location of colitis at an early stage is required to control the symptoms. Changes in redox status, including the production of reactive oxygen and nitrogen species (RONS), have been associated with ulcerative colitis in humans and dextran sodium sulfate (DSS)-induced colitis in rodents. In this study, the in vivo redox status of colons of DSS-induced colitis mice were monitored by Overhauser-enhanced magnetic resonance imaging (OMRI), and the relationship between redox status and colitis development was investigated. Colitis was induced by administering 5% DSS in drinking water to male Slc:ICR mice, which are a strain classified as closed colony outbred mice (5-week-old, 25-30 g). On the 3rd day of the DSS challenge, when no symptoms of colitis were displayed, the contrast decays of N-15-CmP and N-14-CxP tended to show enhancement in the whole colon and were not altered by DMSO. On the 5th day of the DSS challenge, with histological damage of the rectum being displayed, the contrast decay of N-15-CmP was significantly enhanced not only in the rectum, but also in the proximal colon, and this was suppressed by DMSO. On the 7th day of the DSS challenge, with the mice displaying severe colitis symptoms, the image contrasts of N-15-labeled 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (N-15-CmP) and N-14-labeled 3-carboxyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (N-14-CxP) showed much faster decay than those of healthy mice, while the increased decays of both probes were restored by the membrane-permeable reactive oxygen species (ROS) scavenger dimethyl sulfoxide (DMSO). Image differencing between the decay rate images of N-15-CmP and N-14-CxP showed the DSS-induced redox imbalance spreading over the whole colon, and a histogram of the difference image showed a smaller peak and broader distribution with the DSS treatment. These data indicate that ROS are produced intracellularly in the distal and proximal colon in the initiation stage of DSS-induced colitis, and that ROS are produced intracellularly and extracellularly in the advanced stage of DSS-induced colitis.