β 阻断剂对创伤后骨髓的保护作用：G-CSF 的作用。
β-blockade protection of bone marrow following trauma: the role of G-CSF.
机构信息
Department of Surgery, Division of Trauma, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103, USA.
出版信息
J Surg Res. 2011 Oct;170(2):325-31. doi: 10.1016/j.jss.2011.03.059. Epub 2011 Apr 19.
BACKGROUND
Following severe trauma, there is a profound elevation of catecholamine that is associated with a persistent anemic state. We have previously shown that β-blockade (βB) prevents erythroid growth suppression and decreases hematopoietic progenitor cell (HPC) mobilization following injury. Under normal conditions, granulocyte colony stimulating factor (G-CSF) triggers the activation of matrix metalloprotease-9 (MMP-9), leading to the egress of progenitor cells from the bone marrow (BM). When sustained, this depletion of BM cellularity may contribute to BM failure. This study seeks to determine if G-CSF plays a role in the βB protection of BM following trauma.
METHODS
Male Sprague-Dawley rats were subjected to either unilateral lung contusion (LC) ± βB, hemorrhagic shock (HS) ± βB, or both LC/HS ± βB. Propranolol (βB) was given immediately following resuscitation. Animals were sacrificed at 3 and 24 h and HPC mobilization was assessed by evaluating BM cellularity and flow cytometric analysis of peripheral blood for HPCs. The concentration of G-CSF and MMP-9 was measured in plasma by ELISA.
RESULTS
BM cellularity is decreased at 3 h following LC, HS, and LC/HS. HS and LC/HS resulted in significant HPC mobilization in the peripheral blood. The addition of βB restored BM cellularity and reduced HPC mobilization. Three h following HS and LC/HS, plasma G-CSF levels more than double, however LC alone showed no change in G-CSF. βB significantly decreased G-CSF in both HS and LC/HS. Similarly, MMP-9 is elevated following LC/HS, and βB prevents this elevation (390 ± 100 pg/mL versus 275 ± 80 pg/mL).
CONCLUSION
βB protection of the BM following shock and injury may be due to reduced HPC mobilization and maintenance of BM cellularity. Following shock, there is an increase in plasma G-CSF and MMP-9, which is abrogated by βB and suggests a possible mechanism how βB decreases HPC mobilization thus preserving BM cellularity. In contrast, βB protection of BM following LC is not mediated by G-CSF. Therefore, the mechanism of progenitor cell mobilization from the BM is dependent on the type of injury.
背景
严重创伤后，儿茶酚胺水平会显著升高，同时伴有持续的贫血状态。我们之前的研究表明，β 受体阻滞剂（βB）可预防创伤后红细胞生成抑制和造血祖细胞（HPC）动员。在正常情况下，粒细胞集落刺激因子（G-CSF）可触发基质金属蛋白酶-9（MMP-9）的激活，导致祖细胞从骨髓（BM）中移出。当这种骨髓细胞耗竭持续存在时，可能会导致骨髓衰竭。本研究旨在确定 G-CSF 是否在创伤后βB 对 BM 的保护中发挥作用。
方法
雄性 Sprague-Dawley 大鼠接受单侧肺挫伤（LC）±βB、失血性休克（HS）±βB 或 LC/HS 两者均接受βB。复苏后立即给予普萘洛尔（βB）。动物在 3 和 24 小时时处死，并通过评估 BM 细胞密度和外周血中 HPC 的流式细胞术分析来评估 HPC 动员。通过 ELISA 法测量血浆中 G-CSF 和 MMP-9 的浓度。
结果
LC、HS 和 LC/HS 后 3 小时，BM 细胞密度降低。HS 和 LC/HS 导致外周血中 HPC 大量动员。βB 的加入恢复了 BM 细胞密度并减少了 HPC 的动员。HS 和 LC/HS 后 3 小时，血浆 G-CSF 水平增加一倍以上，但单独 LC 则没有 G-CSF 变化。βB 显著降低了 HS 和 LC/HS 中的 G-CSF。同样，LC/HS 后 MMP-9 升高，βB 可预防这种升高（390±100pg/mL 比 275±80pg/mL）。
结论
βB 对休克和损伤后 BM 的保护作用可能是由于减少了 HPC 动员和维持了 BM 细胞密度。休克后，血浆 G-CSF 和 MMP-9 增加，βB 可阻断这种增加，提示βB 减少 HPC 动员从而维持 BM 细胞密度的可能机制。相比之下，βB 对 LC 后 BM 的保护作用不是通过 G-CSF 介导的。因此，祖细胞从 BM 动员的机制取决于损伤类型。
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