白消安对小鼠造血干细胞功能的损伤作用
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(中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家卫生和计划生育委员会人类疾病比较医学重点实验室,北京 100021)

中图分类号:

R-33

基金项目:

国家自然科学基金(81703170);协和青年基金(2017310015);中央科研院所基本业务费(2016ZX310042)


Hematopoietic stem cell injury in mice induced by busulfan
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Affiliation:

(Institute of Laboratory Animal Science,Chinese Academy of Medical Science & Comparative Medicine Center, Peking Union Medical College,Key Laboratory of Human Disease Comparative Medicine,Ministry of Health,Beijing 100021,China)

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    摘要:

    目的 检测不同给药方式对小鼠造血干细胞功能的影响?方法 C57 小鼠,白消安腹腔给药,分为高剂量组(40 mg/ kg)和低剂量组(20 mg/ kg),低剂量组给药一次,高剂量给药组分两天给药,每天给予20 mg/ kg?给药后15 d 和30 d 分别检测小鼠外周血和骨髓细胞计数,造血干细胞,造血祖细胞和长期造血干细胞比例,通过CFU-GM 实验评价小鼠造血祖细胞增殖能力,流式分选长期造血干细胞体外培养,通过单细胞集落实验检测造血干细胞功能?结果 高剂量组和低剂量组白消安均可以降低C57 小鼠外周血中白细胞和血小板数目,降低造血干?祖细胞和长期造血干细胞的比例,降低CFU-GM 和单细胞集落形成能力?高剂量组比低剂量组损伤作用进一步加重?小鼠体重和对照组相比差异无显著性?结论 高剂量组白消安给药15 d 后可以诱导造血干细胞损伤,为造血干细胞损伤机制的探讨和损伤防护的研究提供模型和基础?

    Abstract:

    Objective To study the hematopoietic stem cell injury(HSC) induced by busulfan. Methods C57BL/6 mice were treated with i. p. injection of 20 mg/ kg or 40 mg/ kg busulfan. All mice were euthanized at 15 days and 30 days after busulfan treatment for analysis of the peripheral blood cell counts, bone marrow cellularity and HPC (LKS-, lineage-sca1- c-kit+ ), HSC (LSK, lineage-sca1+ c-kit+ ) and long-term HSC (CD34- LSK, CD34- lineage-sca1 + c-kit+ ) frequency. The colony-forming unit-granulocyte and macrophage (CFU-GM) ability of HPC was measured by colony-forming cell (CFC) assay, and the HSC self-renewal capacity was analyzed by single-cell colony-forming assay. Results The busulfan administration decreased the WBC, RBC and PLT compared with control mice. The HPC function (CFU-GM) was impaired (P < 0.05), and the HSC colony forming ability was decreased at 15 days after busulfan treatment (P < 0.05), whereas the body weight of the mice didn’ t change significantly after busulfan treatment. Conclusions Our findings suggest that busulfan can induce hematopoietic stem cell injury, and provide a support for the study of hematopoietic stem cell injury mechanism.

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李程程,管博文,苏路,党女,王玉全,孟爱民.白消安对小鼠造血干细胞功能的损伤作用[J].中国比较医学杂志,2018,28(2):26~32.

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  • 收稿日期:2017-09-08
  • 在线发布日期: 2018-03-14
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