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免疫损伤介导的骨髓衰竭小鼠模型的建立
  • ISSN号:0253-2727
  • 期刊名称:《中华血液学杂志》
  • 时间:0
  • 分类:R563.1[医药卫生—呼吸系统;医药卫生—临床医学;医药卫生—内科学] R285.5[医药卫生—中药学;医药卫生—中医学]
  • 作者机构:[1]华中科技大学同济医学院附属侧济医院血液内科,武汉430030
  • 相关基金:国家自然科学基金(30570773);教育部博土点基金(20060487061)
中文摘要:

目的对免疫损伤介导的再生障碍性贫血(再障)小鼠模型进行改良研究,为其发病机制和治疗提供研究平台。方法Balb/c小鼠(受鼠)经5.0Gy ^60Co叫射线照射后,输入5×10^6个DBA/2小鼠(供鼠)的淋巴结细胞,观察外周血细胞、骨髓组织切片、骨髓单个核细胞计数、血清IFN-γ水平和调节T细胞(Treg)等指标。结果照射和淋巴结细胞输入可迅速导致Balb/c小鼠外周血三系严重减少,在输入供鼠淋巴结细胞后第14天最低,第28天仍呈三系严重减少,无恢复迹象。第14天骨髓组织切片出现骨髓增生极度减低、造血细胞罕见、脂肪细胞填充等表现,至第28天均未出现改善。血清IFN-γ浓度于第6天[(170.0±17.0)pg/ml]明显升高,为正常水平[(27.7±7.1)pg/m1]的6.3倍,随后逐渐下降至正常;Treg数量先降低,后逐渐上升,第21天[(3.38±0.52)%]基本恢复正常水平[(4.04±0.44)%];在第14天检测Foxp3,与正常对照组比较差异无统计学意义(P〉0.05)。结论通过对受鼠进行放射性核素照射和供鼠淋巴结细胞输注,模型小鼠的各项检测指标均达到骨髓衰竭的诊断标准,符合骨髓衰竭的细胞免疫损伤的发病特点,可作为深入研究骨髓衰竭发病机制及治疗的小鼠模型。

英文摘要:

Objective To establish a mouse model for the study of pathophysiologic mechanism and treatment of borne marrow failure(BMF). Methods Balb/c mice (recipient) were irradiated 5.0 Gy by γ rays of 60^Co, and then infused 5 × 10^6 lymph node(LN) cells from DBA/2 mice (donor) in 4 hours. Pancytopenia was monitored by cell counting, bone marrow damage was assessed by histological staining and mononuclear cell counting. Serum IFN-γ coneentration was measured by ELISA. The proportion of Treg in spleen was detected by flow cytometry. Results h'radiation and infusion of LN cells led to rapid development of severe pancytopenia and BM hypoplasia, which reached the most severity at d14. The pancytopenia remained at d28 and displayed no signs of recovel7. The bone marrow was full of adipose cells with scarcity of hematopoi- etic ceils at d14 and persisted at least for 28 days, being similar to the feature of aplastic anemia. Serum IFN-γ' concentration was 6.3 fold increased [ ( 170.0 ± 17.0) vs ( 27.7 ± 7. 1 ) pg/ml ] at d6. Tregs were decreased after infusion, and then increased [ (3.38 ± 0.52)% ] and recovered to normal [ (4.04± 0.44)% ] at d21. The expression level of the specific transcription factor Foxp3 was similar to normal. Conclusion The MHC antigen of Balb/c mice is identical to that of DBA/2 mice, but their minor antigen differs. 5.0 Gy irradiation and then 5 ×10^6 lymphocyte infusion can induce BMF similar to the features of aplastic anemia.

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期刊信息
  • 《中华血液学杂志》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:天津市南京路288号
  • 邮编:300020
  • 邮箱:cnblood82@yahoo.com.cn
  • 电话:022-27304167
  • 国际标准刊号:ISSN:0253-2727
  • 国内统一刊号:ISSN:12-1090/R
  • 邮发代号:6-54
  • 获奖情况:
  • 中国期刊方阵“双效”期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:25538