Department of Pathology, University of Virginia, Charlottesville, VA, United States of America.
Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America.
Blood Transfus. 2023 Jan;21(1):50-61. doi: 10.2450/2022.0172-22. Epub 2022 Oct 21.
The Red blood cell (RBC) storage lesion results in decreased circulation and function of transfused RBCs. Elevated oxidant stress and impaired energy metabolism are a hallmark of the storage lesion in both human and murine RBCs. Although human studies don't suffer concerns that findings may not translate, they do suffer from genetic and environmental variability amongst subjects. Murine models can control for genetics, environment, and much interventional experimentation can be carried out in mice that is neither technically feasible nor ethical in humans. However, murine models are only useful to the extent that they have similar biology to humans. Hypoxic storage has been shown to mitigate the storage lesion in human RBCs, but has not been investigated in mice.
RBCs from a C57BL6/J mouse strain were stored under normoxic (untreated) or hypoxic conditions (SO2 ~ 26%) for 1h, 7 and 12 days. Samples were tested for metabolomics at steady state, tracing experiments with 1,2,3-C-glucose, proteomics and end of storage post transfusion recovery.
Hypoxic storage improved post-transfusion recovery and energy metabolism, including increased steady state and C-labeled metabolites from glycolysis, high energy purines (adenosine triphosphate) and 2,3-diphospholgycerate. Hypoxic storage promoted glutaminolysis, increased glutathione pools, and was accompanied by elevation in the levels of free fatty acids and acyl-carnitines.
This study isolates hypoxia, as a single independent variable, and shows similar effects as seen in human studies. These findings also demonstrate the translatability of murine models for hypoxic RBC storage and provide a pre-clinical platform for ongoing study.
红细胞（RBC）储存损伤导致输注 RBC 的循环和功能下降。氧化应激升高和能量代谢受损是人类和鼠类 RBC 储存损伤的标志。尽管人体研究不存在发现可能无法转化的问题，但它们确实存在受试者之间遗传和环境变异性的问题。鼠类模型可以控制遗传、环境，并且可以在小鼠中进行许多干预性实验，这些实验在人类中既不可行也不道德。然而，只有当鼠类模型与人类具有相似的生物学特性时，它们才具有实用性。低氧储存已被证明可以减轻人类 RBC 的储存损伤，但尚未在小鼠中进行研究。
来自 C57BL6/J 小鼠品系的 RBC 在常氧（未处理）或低氧条件（SO2~26%）下储存 1h、7 天和 12 天。在稳定状态下对样品进行代谢组学测试，用 1,2,3-C-葡萄糖进行追踪实验，进行蛋白质组学和输注后储存结束时的恢复。
低氧储存改善了输注后的恢复和能量代谢，包括增加了糖酵解的稳态和 C 标记代谢物、高能嘌呤（三磷酸腺苷）和 2,3-二磷酸甘油酸。低氧储存促进了谷氨酰胺分解，增加了谷胱甘肽池，同时伴随着游离脂肪酸和酰基肉碱水平的升高。
本研究将低氧作为单一的独立变量进行分离，并显示出与人类研究中相似的效果。这些发现还证明了低氧 RBC 储存的鼠类模型的可转移性，并为正在进行的研究提供了临床前平台。
