Radiation sequelae is complex and characterized by multiple pathologies, which occur over time and nonuniformly throughout different organs. The study of the mesenteric lymph node (MLN) due to its importance in the gastrointestinal system is of particular interest. Other studies have shown an immediate post-irradiation reduction in cellularity due to the known effects of irradiation on lymphoid cell populations, but the molecular and functional mechanisms that lead to these cellular alterations remain limited. In this work, we show the use of lipidomic, proteomic, and mass spectrometry imaging in the characterization of the effects of acute radiation exposure on the MLN at different time points after ionizing radiation (IR) from 4 d to 21 d after 12 Gy partial body irradiation with 2.5% bone marrow sparing. The combined analyses showed a dysregulation of the lipid and protein composition in the MLN after IR. Protein expression was affected in numerous pathways, including pathways regulating lipids such as LXR/RXR activation and acute phase response. Lipid distribution and abundance was also affected by IR in the MLN, including an accumulation of triacylglycerides, a decrease in polyunsaturated glycerophospholipids, and changes in polyunsaturated fatty acids. Those changes were observed as early as 4 d after IR and were more pronounced for lipids with a higher concentration in the nodules and the medulla of the MLN. These results provide molecular insight into the MLN that can inform on injury mechanism in a non-human primate model of the acute radiation syndrome of the gastrointestinal tract. Those findings may contribute to the identification of therapeutic targets and the development of new medical countermeasures.

中文翻译：

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补充脂质组学、蛋白质组学和质谱成像方法来表征非人类灵长类动物肠系膜淋巴结局部照射后最小骨髓保留的急性辐射效应。

放射后遗症很复杂，其特点是多种病理，随着时间的推移，在不同器官中发生的程度不均匀。由于肠系膜淋巴结 (MLN) 在胃肠道系统中的重要性，因此对其研究特别感兴趣。其他研究表明，由于辐射对淋巴细胞群的已知影响，辐射后细胞结构立即减少，但导致这些细胞改变的分子和功能机制仍然有限。在这项工作中，我们展示了使用脂质组学、蛋白质组学和质谱成像来表征急性辐射暴露在电离辐射（IR）后的不同时间点对 MLN 的影响，即 12 Gy 部分照射后 4 天至 21 天。全身照射，保留 2.5% 骨髓。综合分析显示 IR 后 MLN 中的脂质和蛋白质组成出现失调。蛋白质表达在许多途径中受到影响，包括调节脂质的途径，例如 LXR/RXR 激活和急性期反应。MLN 中的脂质分布和丰度也受到 IR 的影响，包括三酰基甘油酯的积累、多不饱和甘油磷脂的减少以及多不饱和脂肪酸的变化。这些变化早在 IR 后 4 天就观察到，并且对于结节和 MLN 髓质中脂质浓度较高的情况更为明显。这些结果提供了对 MLN 的分子洞察，可以为非人类灵长类动物胃肠道急性辐射综合征模型的损伤机制提供信息。这些发现可能有助于确定治疗靶点和开发新的医疗对策。