From the Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, Florida.
J Trauma Acute Care Surg. 2023 Feb 1;94(2):197-204. doi: 10.1097/TA.0000000000003821. Epub 2022 Oct 31.
Trauma is associated with widespread inflammation, neuroendocrine activation, and an inadequate bone marrow response to anemia. During late-stage erythropoiesis, erythroid progenitors/erythroblasts form clusters on the surface of specialized bone marrow macrophages where they are supported through terminal differentiation and enucleation. We hypothesized that these erythroblastic islands (EBIs) are adversely impacted by severe trauma.
Male Sprague-Dawley rats (n = 8/group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus 2 hours of daily chronic restraint stress (PT/CS), or naive controls. Bone marrow was harvested on days 2 and 7. Nuclear-stained, enriched bone marrow EBIs were fixed and stained for CD71, VCAM-1, and CD163, and confocal images were obtained at 20 times magnification. Numbers of erythroid cells/EBI and ratio of reticulocytes/EBI were counted by a blinded observer. Differences were compared using analysis of variance, with significance defined as p < 0.05.
PT and PT/CS had significantly reduced numbers of erythroid cells per EBI on day 2 when compared with naive (PT: 5.9 ± 1.0 cells [ p < 0.05], PT/CS: 6.8 ± 0.8 cells [ p < 0.05] vs. naive: 8.5 ± 0.8 cells). On day 7, the number of erythroid cells/EBI increased following PT (8.3 ± 0.4 cells) but remained reduced following PT/CS (5.9 ± 0.5 cells [ p < 0.05]). This correlated with an increased proportion of reticulocytes/EBI on day 7 following PT, which was not present following PT/CS (PT: 54% [ p < 0.05] vs. PT/CS: 28%).
Late-stage erythropoiesis was altered following multicompartmental PT early after injury, and these alterations persisted with the addition of daily chronic stress. Alterations in EBI structure and function after severe trauma and critical illness may serve as a promising new area of study to improve mechanistic understanding of persistent anemia after trauma.
创伤与广泛的炎症、神经内分泌激活以及骨髓对贫血的反应不足有关。在晚期红细胞生成过程中，红系祖细胞/成红细胞在骨髓专门巨噬细胞的表面形成簇，在那里通过终末分化和去核得到支持。我们假设这些成红细胞岛（EBI）会受到严重创伤的不利影响。
雄性 Sprague-Dawley 大鼠（每组 8 只）分别接受多发伤（PT）（肺挫伤、失血性休克、盲肠切除术和双侧股骨假性骨折）、PT 加每日慢性束缚应激（PT/CS）或假手术对照。在第 2 天和第 7 天采集骨髓。用核染色法对富含骨髓 EBI 的细胞进行固定和染色，检测 CD71、VCAM-1 和 CD163，并在 20 倍放大倍数下获得共聚焦图像。由一名盲法观察者计数每个 EBI 的红细胞数量和网织红细胞数量与 EBI 的比例。使用方差分析比较差异，以 p < 0.05 为差异有统计学意义。
与假手术组相比，PT 和 PT/CS 在第 2 天的每个 EBI 的红细胞数量明显减少（PT：5.9 ± 1.0 个细胞[ p < 0.05]，PT/CS：6.8 ± 0.8 个细胞[ p < 0.05]，而假手术组：8.5 ± 0.8 个细胞）。第 7 天，PT 后 EBI 的红细胞数量增加（8.3 ± 0.4 个细胞），但 PT/CS 后仍减少（5.9 ± 0.5 个细胞[ p < 0.05]）。这与第 7 天 PT 后网织红细胞数量增加有关，而 PT/CS 后则没有（PT：54%[ p < 0.05] vs. PT/CS：28%）。
创伤后早期多部位 PT 后晚期红细胞生成受到影响，而加入每日慢性应激后这些变化持续存在。严重创伤和危重病后 EBI 结构和功能的改变可能成为改善创伤后持续性贫血的机制理解的一个有前途的新研究领域。
