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亚致死剂量γ-射线全身照射对小鼠造血免疫功能远期影响

Long-term effects of a sublethal γ-ray total body irradiation on the long-term hematopoietic immune function in mice

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【作者】 管博文卢延华苏路路李程程荆学双董银萍王月英李德冠孟爱民

【Author】 GUAN Bowen;LU Yanhua;SU Lulu;LI Chengcheng;JING Xueshuang;DONG Yinping;WANG Yueying;LI Deguan;MENG Aimin;Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences(CAMS);Comparative Medicine Center,Peking Union Medical College(PUMC);NHC Key Laboratory ofHuman Disease Comparative Medicine;Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases;Institute of Radiation Medicine,Chinese Academy of Medical Science(CAMS) and Peking Union Medical College(PUMC);Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine;

【通讯作者】 李德冠;孟爱民;

【机构】 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健康委员会人类疾病比较医学重点实验室北京市人类重大疾病实验动物模型工程技术研究中心中国医学科学院/北京协和医学院放射医学研究所天津市放射医学与分子核医学重点实验室

【摘要】 目的观察4 Gy、6 Gy全身照射后6个月C57BL/6 J小鼠的造血和免疫等功能指标变化。方法对8~12周的C57BL/6 J小鼠分别进行4 Gy和6 Gy全身照射,照射6个月后检测外周血细胞计数及分类、胸腺系数及脾系数、外周血及脾免疫细胞分型、脾T细胞p16表达水平。结果照射后6个月外周血白细胞、红细胞计数仍然明显低于对照组。血小板与对照组无明显差异。外周血细胞分类结果显示照射组小鼠中性粒细胞比例升高、淋巴细胞比例下降,呈现细胞分化偏移现象。与对照组相比,6 Gy照射后6个月,胸腺系数明显降低(P<0. 05)。脾系数无差异。外周血流式分析,结果显示4 Gy、6 Gy照射后,B淋巴细胞、NK细胞仍然低于对照组,提示受照后6个月未完全恢复。受照组CD4比例高于对照组。CD8、单核细胞与对照组未见差异。脾免疫细胞进行流式分析,结果显示4 Gy和6 Gy照射后6个月,B220对于对照组均有明显下降,均具极显著性差异(P<0. 01)。相比于对照组,6 Gy组脾T细胞p16表达有升高的趋势,但无显著性差异。结论亚致死剂量照射后6个月各项检测基本恢复,但是外周血分类中性粒持续升高,胸腺系数及外周血、脾B淋巴细胞比例仍低于对照组。提示可能有远期损伤。本项实验数据为中高剂量照射后造血免疫功能长期损伤研究提供了基础数据。

【Abstract】 Objective To observe the changes in hematopoietic and immune function at 6 months post 4 Gy or 6 Gy γ-ray total body irradiation( TBI) in C57 BL/6 J mice. Methods C57 BL/6 J mice of 8-12 weeks of age were irradiated with 4 Gy or 6 Gy TBI. At 6 months after irradiation exposure,the peripheral blood cell count and classification,immune organ coefficient,immune phenotyping of the peripheral blood and spleen cells,and expression level of splenic T cell p16 were detected. Results Six months after irradiation exposure,the peripheral blood leukocyte and red blood cell count in the mice exposed to TBI remained significantly lower than those in the control group. There was no significant difference in the count of platelets in the irradiated mice compared to the control group. The result of the peripheral blood cell classification showed that the proportion of neutrophils in the irradiated mice group increased and the proportion of lymphocytes decreased,indicating a skew in blood cell differentiation. Compared with the control group,the thymus coefficient in the irradiated mice was significantly decreased at 6 months post 6 Gy TBI( P<0. 05). There was no significant difference in the spleen coefficient. Phenotyping of the peripheral blood cells was performed by flow cytometry. The result showed that the proportion of B lymphocytes and NK cells in the irradiated mice remained lower than those in the control group,while the proportion of CD4 lymphocytes in the irradiated group was higher than that in the control group. There was no significant difference between CD8 lymphocytes and monocyte levels in the irradiated group compared with the control group. The proportion of B220 cells was clearly decreased in the irradiated mice compared with the control group based on the splenic immune phenotyping assay( P<0. 01). Compared with the control group,the expression of p16 in the splenic T cells of the 6 Gy TBI mice was increased but not significantly( P > 0. 05). Conclusions Hematopoietic immune phenotyping indicated the recovery at 6 months after the sublethal dose of TBI but the neutrophils in the peripheral blood continued to be increased,and the thymus coefficient and the proportion of B lymphocytes in the peripheral blood and spleen were still lower than those in the control group,suggesting a long-term injury. These experimental result provide basic data for the study of total body irradiation-induced long-term injury of hematopoietic immune function.

【基金】 国家自然科学基金(81372928,81573094);国家自然科学基金(81703170);中国医学科学院医学与健康科技创新工程(2017-I2M-3-015);国家重点研发计划(2017YFA0105200)
  • 【文献出处】 中国比较医学杂志 ,Chinese Journal of Comparative Medicine , 编辑部邮箱 ,2019年11期
  • 【分类号】R818;R-332
  • 【被引频次】3
  • 【下载频次】84
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