γ-生育三烯酚可保护全身照射后的小鼠造血干细胞和祖细胞。

Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation.

机构信息

a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889, USA.

出版信息

Radiat Res. 2010 Jun;173(6):738-47. doi: 10.1667/RR1824.1.

DOI:10.1667/RR1824.1

PMID:20518653

Abstract

We analyzed the radioprotective effects of gamma-tocotrienol (GT3) on hematopoietic stem cells (HSCs) and progenitor cells (HPCs) in sublethally irradiated mice. Flow cytometry analysis indicated that radiation depleted HPCs (c-Kit(+), Lin(-)) to 40% at days 2 and 4 after total-body irradiation (TBI) in all treatment groups. The HPC numbers in GT3-treated mice recovered almost completely (90%) at day 7 but remained depleted in vehicle-treated mice (30%) even at day 13 after TBI. An in vitro colony-forming assay on sorted HSCs (Lin(-), Sca1(+), c-Kit(+)) indicated that TBI reduced the number of colonies to 40% and 50% at day 17 and 60, respectively, in vehicle-treated groups compared to unirradiated controls (naïve). GT3-treated irradiated mice maintained higher numbers of colonies (86% and 80% compared to naïve mice), thereby preserving the self-renewable capacity of HSCs. Histopathology of sternal bone marrow indicated more regenerative microfoci for myeloid cells and megakaryocytes and higher overall cellularity in GT3-treated mice compared to vehicle controls at days 7 and 13 after TBI. GT3 treatment also reduced the frequency of micronucleated erythrocytes significantly in irradiated mice. Our results demonstrate that GT3 protected hematopoietic tissue by preserving the HSCs and HPCs and by preventing persistent DNA damage.

摘要

我们分析了γ-生育三烯酚（GT3）对亚致死剂量全身照射（TBI）小鼠造血干细胞（HSCs）和祖细胞（HPCs）的放射防护作用。流式细胞术分析表明，在 TBI 后第 2 和第 4 天，所有治疗组的 HPCs（c-Kit（+），Lin（-））减少了 40%。GT3 处理组的 HPC 数量在第 7 天几乎完全恢复（90%），而在 TBI 后第 13 天，载体处理组仍减少（30%）。对分选的 HSCs（Lin（-），Sca1（+），c-Kit（+））进行的体外集落形成试验表明，与未照射对照（naïve）相比，TBI 使载体处理组的集落数量在第 17 天和第 60 天分别减少了 40%和 50%。GT3 处理的照射小鼠维持了更高数量的集落（与未照射对照相比，分别为 86%和 80%），从而保持了 HSCs 的自我更新能力。胸骨骨髓组织病理学表明，与载体对照相比，GT3 处理的照射小鼠在 TBI 后第 7 天和第 13 天具有更多的髓系细胞和巨核细胞再生微焦点，以及更高的总体细胞数。GT3 处理还显著降低了照射小鼠中微核红细胞的频率。我们的结果表明，GT3 通过保护 HSCs 和 HPCs 并防止持续的 DNA 损伤来保护造血组织。