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代谢重编程可提升血库条件下储存的红细胞的循环功能。

Metabolic rejuvenation upgrades circulatory functions of red blood cells stored under blood bank conditions.

机构信息

Université de Paris, UMR_S1134, BIGR, INSERM, Paris, France.

Institut National de la Transfusion Sanguine, Paris, France.

出版信息

Transfusion. 2021 Mar;61(3):903-918. doi: 10.1111/trf.16245. Epub 2020 Dec 31.

DOI:10.1111/trf.16245
PMID:33381865
Abstract

BACKGROUND

Red blood cells (RBC) change upon hypothermic conservation, and storage for 6 weeks is associated with the short-term clearance of 15% to 20% of transfused RBCs. Metabolic rejuvenation applied to RBCs before transfusion replenishes energetic sources and reverses most storage-related alterations, but how it impacts RBC circulatory functions has not been fully elucidated.

STUDY DESIGN AND METHODS

Six RBC units stored under blood bank conditions were analyzed weekly for 6 weeks and rejuvenated on Day 42 with an adenine-inosine-rich solution. Impact of storage and rejuvenation on adenosine triphosphate (ATP) levels, morphology, accumulation of storage-induced microerythrocytes (SMEs), elongation under an osmotic gradient (by LORRCA), hemolysis, and phosphatidylserine (PS) exposure was evaluated. The impact of rejuvenation on filterability and adhesive properties of stored RBCs was also assessed.

RESULTS

Rejuvenation of RBCs restored intracellular ATP to almost normal levels and decreased the PS exposure from 2.78% to 0.41%. Upon rejuvenation, the proportion of SME dropped from 28.2% to 9.5%, while the proportion of normal-shaped RBCs (discocytes and echinocytes 1) increased from 47.7% to 67.1%. In LORCCA experiments, rejuvenation did not modify the capacity of RBCs to elongate and induced a reduction in cell volume. In functional tests, rejuvenation increased RBC filterability in a biomimetic splenic filter (+16%) and prevented their adhesion to endothelial cells (-87%).

CONCLUSION

Rejuvenation reduces the proportion of morphologically altered and adhesive RBCs that accumulate during storage. Along with the improvement in their filterability, these data show that rejuvenation improves RBC properties related to their capacity to persist in circulation after transfusion.

摘要

背景

低温保存会导致红细胞(RBC)发生变化,储存 6 周会导致输注的 RBC 在短期内清除 15%至 20%。在输血前对 RBC 进行代谢再激活可补充能量来源并逆转大多数与储存相关的改变,但它如何影响 RBC 的循环功能尚未完全阐明。

研究设计和方法

将 6 个在血库条件下储存的 RBC 单位每周分析一次,共 6 周,并在第 42 天用富含腺嘌呤和肌苷的溶液进行再激活。评估储存和再激活对三磷酸腺苷(ATP)水平、形态、储存诱导的微小红细胞(SME)积累、渗透压梯度下的伸长(通过 LORRCA)、溶血和磷脂酰丝氨酸(PS)暴露的影响。还评估了再激活对储存 RBC 过滤性和黏附特性的影响。

结果

RBC 的再激活将细胞内 ATP 恢复到几乎正常水平,并将 PS 暴露从 2.78%降低到 0.41%。再激活后,SME 的比例从 28.2%下降到 9.5%,而正常形态 RBC(圆盘和棘红细胞 1)的比例从 47.7%上升到 67.1%。在 LORCCA 实验中,再激活并未改变 RBC 伸长的能力,并导致细胞体积减小。在功能测试中,再激活增加了 RBC 在仿生脾脏过滤器中的过滤性(增加 16%),并防止其黏附内皮细胞(减少 87%)。

结论

再激活减少了储存过程中形态改变和黏附 RBC 的比例。再激活提高了 RBC 的过滤性,并改善了它们的特性,这表明其提高了 RBC 在输血后在循环中持续存在的能力。

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