Gamma-Tocotrienol Protects Hematopoietic Stem and Progenitor Cells in Mice after Total-Body Irradiation
Gamma-Tocotrienol Protects Hematopoietic Stem and Progenitor Cells in Mice after Total-Body Irradiation
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DOI：
10.1667/rr1824.1
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发表时间：
2010-06-01
影响因子：
3.4
通讯作者：
Kumar, K. Sree
中科院分区：
文献类型：
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作者：
Kulkarni, Shilpa;Ghosh, Sanchita P.;Kumar, K. Sree
我们分析了γ-生育三烯酚（GT 3）对亚致死剂量照射小鼠造血干细胞（HSC）和祖细胞（HPC）的辐射防护作用。流式细胞术分析表明，在所有治疗组中，在全身照射（TBI）后第2天和第4天，照射耗尽HPC（c-Kit（+），Lin（-））至40%。GT3处理的小鼠中的HPC数量在第7天几乎完全恢复（90%），但即使在TBI后第13天，载体处理的小鼠中的HPC数量仍保持耗尽（30%）。对分选的HSC（Lin（-）、Sca 1（+）、c-Kit（+））的体外集落形成测定表明，与未照射的对照（幼稚）相比，在载体处理组中，TBI在第17天和第60天分别将集落数量减少至40%和50%。GT3处理的辐射小鼠保持了更高数量的集落（与幼稚小鼠相比为86%和80%），从而保留了HSC的自我再生能力。胸骨骨髓的组织学显示，在TBI后第7天和第13天，与载体对照相比，GT3处理的小鼠中骨髓细胞和巨核细胞的再生微灶更多，总体细胞构成更高。GT3处理还显著降低了辐射小鼠中微核红细胞的频率。我们的研究结果表明，GT3通过保存HSC和HPC以及防止持续的DNA损伤来保护造血组织。(C)2010年，辐射研究学会
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 (naive). GT3-treated irradiated mice maintained higher numbers of colonies (86% and 80% compared to naive 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. (C) 2010 by Radiation Research Society