Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells
Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells
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DOI：
10.3324/haematol.2015.139139
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发表时间：
2016-05-01
期刊：
影响因子：
10.1
通讯作者：
Zimring, James C.
中科院分区：
文献类型：
--
作者：
de Wolski, Karen;Fu, Xiaoyoun;Zimring, James C.
红细胞输注是一种非常常见的住院手术，在美国，每年有超过70人中有1人接受红细胞输注。然而，储存的红细胞是一种非均匀的产品，基于红细胞储存生物学中的供体与供体的差异。虽然红细胞在储存过程中有数千个生物学参数发生变化，但仍不清楚哪些变化与红细胞的功能相关，而不是偶然的变化。在本报告中，红细胞储存/输血的小鼠模型应用于13种遗传上不同的小鼠品系，并结合高分辨率代谢组学来鉴定与储存后红细胞循环相关的代谢变化。一般的氧化，特别是脂质的过氧化，出现了与极端统计学显著性相关的变化，包括二羧酸和单羟基脂肪酸的生成。此外，抗氧化途径的差异，已知调节脂质膜上的氧化应激被确定。最后，确定了在采集血液时不同的代谢物，并预测了红细胞在储存后的表现，从而有可能在采集时筛选供体。总之，这些发现为理解红细胞储存期间的代谢变化绘制了一幅新的图景，因为它们与红细胞循环有关。
Transfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation.