Acetylsalicylic Acid Reduces the Severity of Dextran Sodium Sulfate-Induced Colitis and Increases the Formation of Anti-Inflammatory Lipid Mediators
Acetylsalicylic Acid Reduces the Severity of Dextran Sodium Sulfate-Induced Colitis and Increases the Formation of Anti-Inflammatory Lipid Mediators
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DOI：
10.1155/2013/748160
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Weylandt, Karsten H.
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文献类型：
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作者：
Koehnke, Thomas;Gomolka, Beate;Weylandt, Karsten H.
非甾体抗炎药在炎症性肠病中的作用是有争议的，因为它们与疾病加重有关。与其他环氧合酶抑制剂不同，乙酰水杨酸（阿萨）可增强源自花生四烯酸的抗炎和促消退脂氧素以及源自ω-3多不饱和脂肪酸（如二十二碳六烯酸（DHA））的消退素的形成。在这项研究中，我们研究了阿萨对小鼠葡聚糖硫酸钠结肠炎的影响。使用小鼠磁共振成像（MRI）方案和尸检评估来评估疾病严重程度，并使用液相色谱-串联质谱法测量脂质代谢产物。在阿萨处理的小鼠中，通过表型和MRI评估证明结肠炎活动降低，并在尸检分析中得到证实。脂质介质分析显示，阿萨治疗后，脂氧素A4持续形成，DHA衍生的17-羟基二十二碳六烯酸（17-HDHA）增加。此外，在RAW264.7小鼠巨噬细胞中的体外实验表明，与17-HDHA孵育后，吞噬活性显著增加，支持其促分解作用。这些结果表明阿萨在小鼠结肠炎模型中具有保护作用，并可能为炎症性肠病患者（特别是溃疡性结肠炎患者）仔细重新评估阿萨治疗提供依据，可能与DHA补充剂联合使用。
The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.