Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis
Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis
复制标题
Maresin1 减轻脓毒症小鼠的代谢功能障碍：基于 1H NMR 的代谢组学分析
DOI：
10.1155/2019/2309175
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Jin, Sheng-Wei
中科院分区：
文献类型：
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作者：
Hao, Yu;Zheng, Hong;Jin, Sheng-Wei
Maresin 1（MaR 1）是一种新型的抗炎和促分解脂质介质，已被证明在脓毒症动物模型中发挥器官保护作用。然而，潜在的机制仍然没有完全阐明。在这项研究中，我们试图探索MaR 1对盲肠结扎穿孔（CLP-）诱导的脓毒症小鼠代谢功能障碍的影响。我们发现，MaR 1显着增加了脓毒症小鼠的总生存率和减轻肺和肝损伤。此外，MaR 1显着降低促炎细胞因子（TNF-α和IL-6）的水平，减轻线粒体损伤。基于H-1 NMR的代谢组学分析显示，CLP诱导的脓毒症小鼠血清中乙酸盐、丙酮酸盐和乳酸盐水平升高，肺中丙氨酸、天冬氨酸盐、谷氨酸盐和富马酸盐水平降低。然而，这些代谢紊乱，主要涉及能量和氨基酸代谢，可以通过MaR 1治疗恢复。因此，我们的研究结果表明，MaR 1对脓毒症的保护作用可能与代谢功能障碍的恢复以及炎症和线粒体损伤的减轻有关。
Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF- and IL-6) and alleviated mitochondrial damage. Based on a H-1 NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.