持续性损伤相关贫血与衰老：新的认识。
Persistent injury-associated anemia and aging: Novel insights.
机构信息
From the Department of Surgery and Sepsis and Critical Illness Research Center (T.J.L., K.B.K., J.C.M., S.C.B., C.L., P.A.E., A.M.M.), University of Florida Health, Gainesville, Florida; Institute on Aging (C.S.C., C.L.), University of Florida Health, Gainesville, Florida; and College of Liberal Arts and Sciences (J.M.P.), University of Florida, Gainesville, Florida.
出版信息
J Trauma Acute Care Surg. 2018 Mar;84(3):490-496. doi: 10.1097/TA.0000000000001766.
BACKGROUND
Hypercatecholaminemia and bone marrow dysfunction have been implicated in the pathophysiology of persistent injury-associated anemia. The elderly may be more vulnerable to bone marrow dysfunction due to high basal and peak catecholamine levels and impaired hematopoietic progenitor growth. We hypothesized that aging would adversely affect persistent injury-associated anemia.
METHODS
Male Sprague-Dawley rats aged 8 to 9 weeks and F344-BN rats aged 25 months were randomized to naive controls, lung contusion plus hemorrhagic shock (LCHS), and LCHS plus daily chronic restraint stress (LCHS/CS). Urine norepinephrine was measured on Days 1 and 7. Mobilization of hematopoietic progenitor cells (HPCs), bone marrow colony-forming units-erythroid growth, and peripheral blood hemoglobin, mean corpuscular volume (MCV), and red cell distribution width (RDW) were assessed on Day 7 (*p < 0.05 young vs. aged counterpart by one-way analysis of variance).
RESULTS
Aged rats had higher norepinephrine levels at naive baseline (97* vs. 27 ng/mL) and 7 days following LCHS/CS when compared with young (359* vs. 127 ng/mL). Following LCHS/CS, HPC mobilization was greater among young rats when compared with aged (5.4 vs. 2.5%). Colony-forming units-erythroid growth was lower among aged animals for each group (naive: 47* vs. 65; LCHS: 40* vs. 50; LCHS/CS: 38* vs. 44 cells/plate). Aged naive rats had higher initial hemoglobin (15.2* vs. 14.3 g/dL) but lower MCV (48* vs. 59 fL/cell) and larger RDW at baseline and greater differences 7 days after LCHS/CS (MCV: 46* vs. 60 fL/cell; RDW: 17.4* vs. 16.3%).
CONCLUSIONS
Compared with young rats, aged rats had less HPC mobilization despite elevated basal and peak norepinephrine. Aged rats were disproportionately affected by impaired hematopoietic progenitor growth and an iron-restricted red blood cell phenotype at baseline, which persisted 7 days after injury. Further research is needed to assess how the clinical approach to persistent injury-associated anemia should differ for elderly trauma patients.
背景
高儿茶酚胺血症和骨髓功能障碍与持续性创伤相关贫血的病理生理学有关。老年人由于基础和峰值儿茶酚胺水平较高以及造血祖细胞生长受损，可能更容易受到骨髓功能障碍的影响。我们假设衰老将对持续性创伤相关贫血产生不利影响。
方法
将 8 至 9 周龄的雄性 Sprague-Dawley 大鼠和 25 月龄的 F344-BN 大鼠随机分为正常对照组、肺挫伤合并失血性休克（LCHS）组和 LCHS 合并每日慢性束缚应激（LCHS/CS）组。在第 1 天和第 7 天测量尿去甲肾上腺素。在第 7 天评估造血祖细胞（HPC）动员、骨髓集落形成单位-红细胞生长以及外周血血红蛋白、平均红细胞体积（MCV）和红细胞分布宽度（RDW）（*p < 0.05 青年 vs. 老年同龄对照通过单向方差分析）。
结果
与年轻大鼠相比，老年大鼠在基础状态下（97与 27ng/mL）和 LCHS/CS 后第 7 天的去甲肾上腺素水平更高（359与 127ng/mL）。与年轻大鼠相比，LCHS/CS 后 HPC 动员在年轻大鼠中更大（5.4与 2.5%）。每个组的红细胞生成集落形成单位生长都较低（正常：47与 65；LCHS：40与 50；LCHS/CS：38与 44 个/板）。在基线时，老年正常大鼠的初始血红蛋白水平较高（15.2与 14.3g/dL），但 MCV 较低（48与 59fL/细胞），RDW 较大，在 LCHS/CS 后 7 天差异更大（MCV：46与 60fL/细胞；RDW：17.4与 16.3%）。
结论
与年轻大鼠相比，尽管基础和峰值去甲肾上腺素升高，但老年大鼠的 HPC 动员减少。在基线时，老年大鼠造血祖细胞生长受损和铁限制的红细胞表型受到不成比例的影响，在创伤后 7 天仍持续存在。需要进一步研究以评估老年人创伤患者持续性创伤相关贫血的临床治疗方法应如何有所不同。
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