辐射导致长期骨髓抑制的研究进展

李德冠 樊赛军 孟爱民

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辐射导致长期骨髓抑制的研究进展

    通讯作者: 孟爱民, email:ai_min_meng@126.com
  • 基金项目:

    天津自然科学基金(项目编号:12JCQNJC09100,15JCZDJC35200)

    国家自然科学基金(81372928,81102873)

    国家重点基础研究发展计划(2011CB964800-G)

Long-term myelosuppression induced by irradiation

    Corresponding author: Meng Aimin, email:ai_min_meng@126.com
  • 摘要: 随着接受放疗患者生存期的延长,患者发生长期骨髓抑制的概率也大幅提高。长期骨髓抑制在临床中常被忽略,随着时间延长患者病情会逐渐加重,生活质量降低。许多长期骨髓抑制患者会形成再生障碍性贫血或者骨髓增生异常综合征,严重者可引发死亡。研究资料表明,活性氧和丝裂原活化蛋白激酶p38(P38MAPK)通路在辐射诱导长期骨髓抑制中占主要作用。笔者总结了辐射导致的长期骨髓抑制的相关研究,指出了今后的研究方向。
  • [1] Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014[J]. CA Cancer J Clin, 2014, 64(1):9-29.
    [2] Shao L, Luo Y, Zhou D. Hematopoietic stem cell injury induced by ionizing radiation[J]. Antioxid Redox Signal, 2014, 20(9):1447-1462.
    [3] Shao L, Sun Y, Zhang Z, et al. Deletion of proapoptotic Puma selec-tively protects hematopoietic stem and progenitor cells against high-dose radiation[J]. Blood, 2010, 115(23):4707-4714.
    [4] Mohrin M, Bourke E, Alexander D, et al. Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis[J]. Cell Stem Cell, 2010, 7(2):174-185.
    [5] Yu H, Shen H, Yuan Y, et al. Deletion of Puma protects hematopoi-etic stem cells and confers long-term survival in response to high-dose gamma-irradiation[J]. Blood, 2010, 115(17):3472-3480.
    [6] Carbonneau CL, Despars G, Rojas-Sutterlin S, et al. Ionizing radia-tion-induced expression of INK4a/ARF in murine bone marrow-de-rived stromal cell populations interferes with bone marrow home-ostasis[J]. Blood, 2012, 119(3):717-726.
    [7] Wang Y, Schulte BA, LaRue AC, et al. Total body irradiation se-lectively induces murine hematopoietic stem cell senescence[J]. Blood, 2006, 107(1):358-366.
    [8] Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells[J]. Nature, 2003, 423(6937):302-305.
    [9] Molofsky AV, He S, Bydon M, et al. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence path-ways[J]. Genes Dev, 2005, 19(12):1432-1437.
    [10] Lessard J, Sauvageau G. Bmi-1 determines the proliferative capaci-ty of normal and leukaemic stem cells[J]. Nature, 2003, 423(6937):255-260.
    [11] Spangrude GJ, Brooks DM, Tumas DB. Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells:in vivo expansion of stem cell phenotype but not func-tion[J]. Blood, 1995, 85(4):1006-1016.
    [12] Meng A, Wang Y, Brown SA, et al. Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apopto-sis-dependent and -independent mechanisms[J]. Exp Hematol, 2003, 31(12):1348-1356.
    [13] Meng A, Wang Y, Van Zant G, et al. Ionizing radiation and busul-fan induce premature senescence in murine bone marrow hematopoietic cells[J]. Cancer Res, 2003, 63(17):5414-5419.
    [14] Wang Y, Liu L, Pazhanisamy SK, et al. Total body irradiation caus-es residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells[J]. Free Radic Biol Med, 2010, 48(2):348-356.
    [15] Bigarella CL, Liang R, Ghaffari S. Stem cells and the impact of ROS signaling[J]. Development, 2014, 141(22):4206-4218.
    [16] Ito K, Hirao A, Arai F, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells[J]. Nature, 2004, 431(7011):997-1002.
    [17] Ito K, Takubo K, Arai F, et al. Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes[J]. J Immunol, 2007, 178(1):103-110.
    [18] Lewandowski D, Barroca V, Duconge F, et al. In vivo cellular imag-ing pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution[J]. Blood, 2010, 115(3):443-452.
    [19] Abbas HA, Maccio DR, Coskun S, et al. Mdm2 is required for sur-vival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity[J]. Cell Stem Cell, 2010, 7(5):606-617.
    [20] Miyamoto K, Araki KY, Naka K, et al. Foxo3a is essential for main-tenance of the hematopoietic stem cell pool[J]. Cell Stem Cell, 2007, 1(1):101-112.
    [21] Chen C, Liu Y, Liu R, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species[J]. J Exp Med, 2008, 205(10):2397-2408.
    [22] Shao L, Wang Y, Chang J, et al. Hematopoietic stem cell senes-cence and cancer therapy-induced long-term bone marrow injury[J]. Transl Cancer Res, 2013, 2(5):397-411.
    [23] Zhang H, Zhai Z, Wang Y, et al. Resveratrol ameliorates ionizing ir-radiation-induced long-term hematopoietic stem cell injury in mice[J]. Free Radic Biol Med, 2013, 54:40-50.
    [24] Li H, Wang Y, Pazhanisamy SK, et al. Mn (Ⅲ) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-in-duced long-term bone marrow suppression[J]. Free Radic Biol Med, 2011, 51(1):30-37.
    [25] Luo Y, Li L, Zou P, et al. Rapamycin enhances long-term hematopoi-etic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence[J]. Transplantation, 2014, 97(1):20-29.
    [26] Li D, Lu L, Zhang J, et al. Mitigating the effects of Xuebijing injec-tion on hematopoietic cell injury induced by total body irradiation with gamma rays by decreasing reactive oxygen species levels[J]. Int J Mol Sci, 2014, 15(6):10541-10553.
    [27] 李德冠樊飞跃, 孟爱民. p38 MAPK通路在造血系统调节中的作用[J]. 中国药理学通报, 2011, 27(1):4-6.
    [28] Geest CR, Coffer PJ. MAPK signaling pathways in the regulation of hematopoiesis[J]. J Leukoc Biol, 2009, 86(2):237-250.
    [29] Navas TA, Mohindru M, Estes M, et al. Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors[J]. Blood, 2006, 108(13):4170-4177.
    [30] Zhou L, Opalinska J, Verma A. p38 MAP kinase regulates stem cell apoptosis in human hematopoietic failure[J]. Cell Cycle, 2007, 6(5):534-537.
    [31] Tothova Z, Kollipara R, Huntly BJ et al. FoxOs are critical media-tors of hematopoietic stem cell resistance to physiologic oxidative stress[J]. Cell, 2007, 128(2):325-339.
    [32] Wang Y, Liu L, Zhou D. Inhibition of p38 MAPK attenuates ioniz-ing radiation-induced hematopoietic cell senescence and residual bone marrow injury[J]. Radiat Res, 2011, 176(6):743-752.
    [33] Li D, Wang Y, Wu H, et al. Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administra-tion[J]. J Radiat Res, 2011, 52(6):712-716.
    [34] 李德冠, 路璐, 吴红英, 等. G-CSF联合SB203580对4 Gy照射小鼠免疫系统的作用[J]. 国际放射医学核医学杂志, 2014, 38(4):216-218.
    [35] Shao L, Feng W, Li H, et al. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a-and Arf-independent manner[J]. Blood, 2014, 123(20):3105-3115.
    [36] Geiger H. HSC senescence upon irradiation[J]. Blood, 2014, 123(20):3060-3061.
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  • 收稿日期:  2015-03-03

辐射导致长期骨髓抑制的研究进展

    通讯作者: 孟爱民, email:ai_min_meng@126.com
  • 中国医学科学院放射医学研究所, 天津市放射医学和分子核医学重点实验室, 天津, 300192
基金项目:  天津自然科学基金(项目编号:12JCQNJC09100,15JCZDJC35200)国家自然科学基金(81372928,81102873)国家重点基础研究发展计划(2011CB964800-G)

摘要: 随着接受放疗患者生存期的延长,患者发生长期骨髓抑制的概率也大幅提高。长期骨髓抑制在临床中常被忽略,随着时间延长患者病情会逐渐加重,生活质量降低。许多长期骨髓抑制患者会形成再生障碍性贫血或者骨髓增生异常综合征,严重者可引发死亡。研究资料表明,活性氧和丝裂原活化蛋白激酶p38(P38MAPK)通路在辐射诱导长期骨髓抑制中占主要作用。笔者总结了辐射导致的长期骨髓抑制的相关研究,指出了今后的研究方向。

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