Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Integr Biol (Camb). 2014 Jan;6(1):65-75. doi: 10.1039/c3ib40187a.
The most recent American Association of Blood Banks survey found that 40,000 units of blood are required daily for general medicine, hematology/oncology, surgery, and for accident and trauma victims. While blood transfusions are an extremely important component of critical healthcare, complications associated with transfusion of blood components still exist. It is well-established that the red blood cell (RBC) undergoes many physical and chemical changes during storage. Increased oxidative stress, formation of advanced glycation endproducts, and microparticle formation are all known to occur during RBC storage. Furthermore, it is also known that patients who receive a transfusion have reduced levels of available nitric oxide (NO), a major determinant in blood flow. However, the origin of this reduced NO bioavailability is not completely understood. Here, we show that a simple modification to the glucose concentration in the solutions used to process whole blood for subsequent RBC storage results in a remarkable change in the ability of these cells to stimulate NO. In a controlled in vitro microflow system, we discovered that storage of RBCs in normoglycemic versions of standard storage solutions resulted in RBC-derived ATP release values 4 weeks into storage that were significantly greater than day 1 release values for those RBCs stored in conventional solutions. During the same storage duration, microfluidic technologies enabled measurements of endothelium-derived NO that were stimulated by the ATP release from the stored RBCs. In comparison to currently accepted processing solutions, the NO production increased by more than 25% in the presence of the RBCs stored in the normoglycemic storage solutions. Control experiments using inhibitors of ATP release from the RBCs, or ATP binding to the endothelium, strongly suggest that the increased NO production by the endothelium is directly related to the ability of the stored RBCs to release ATP. We anticipate these findings to represent a starting point in controlling glucose levels in solutions used for blood component storage, especially considering that current solutions contain glucose at levels that are nearly 20-fold greater than blood glucose levels of a healthy human, and even 10-fold greater than levels found in diabetic bloodstreams.
最近的美国血库协会调查发现，每天需要 4 万单位的血液用于普通医学、血液学/肿瘤学、外科手术以及事故和创伤患者。虽然输血是重症医疗保健的一个极其重要的组成部分，但与输血相关的并发症仍然存在。众所周知，红细胞（RBC）在储存过程中会经历许多物理和化学变化。在 RBC 储存过程中，已知会发生氧化应激增加、晚期糖基化终产物形成和微粒形成。此外，也已知接受输血的患者的可用一氧化氮（NO）水平降低，NO 是血流的主要决定因素。然而，这种降低的 NO 生物利用度的来源尚不完全清楚。在这里，我们表明，简单地修改用于处理全血以随后储存 RBC 的溶液中的葡萄糖浓度，可导致这些细胞刺激 NO 的能力发生显著变化。在受控的体外微流系统中，我们发现，在标准储存溶液的正常血糖版本中储存 RBC 会导致储存 4 周后 RBC 衍生的 ATP 释放值显著大于那些储存在常规溶液中的 RBC 第 1 天的释放值。在相同的储存期间，微流控技术使能够测量由储存 RBC 释放的 ATP 刺激的内皮衍生的 NO。与目前接受的处理溶液相比，在储存于正常血糖储存溶液中的 RBC 存在的情况下，NO 产量增加了 25%以上。使用 RBC 从 ATP 释放的抑制剂或 ATP 与内皮结合的对照实验强烈表明，内皮中 NO 产量的增加与储存 RBC 释放 ATP 的能力直接相关。我们预计这些发现将成为控制血液成分储存中使用的溶液中葡萄糖水平的起点，特别是考虑到目前的溶液中葡萄糖的含量几乎是健康人血糖水平的 20 倍，甚至是糖尿病患者血液中葡萄糖水平的 10 倍。
