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粒细胞集落刺激因子减轻小鼠混合骨髓移植后移植物抗宿主病的实验研究 被引量:1

Experimental study of G-CSF alleviating graft-versus-host disease after mixed bone marrow transplantation
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摘要  目的 探讨同基因骨髓混合一定比例粒细胞集落刺激因子(G CSF)动员的异基因骨髓移植能否减轻急性移植物抗宿主病(aGVHD)。方法 将BALB/c与BCF1(BALB/c×C57BL/6)小鼠或与G CSF动员 BCF1 小鼠脾细胞按一定比例混合,腹腔注入 BALB/c 幼鼠,制备新生小鼠GVHD模型,结果以脾指数表示。成年雌性 BALB/c小鼠接受60 Co全身照射8.5Gy后进行移植,移植物为BALB/c与雄性BCF1 或与G CSF动员 BCF1 小鼠骨髓细胞按一定比例的混合,移植细胞总数60×105 个/只。观察移植小鼠aGVHD典型症状、病理表现及存活率。ELISA法测定细胞因子含量,流式细胞术分析T细胞亚群变化。结果 (1)注射BALB/c与BCF1 小鼠脾细胞混合比例为2∶1、1∶1及异基因BCF1 小鼠脾细胞的新生小鼠均发生GVHD;但G CSF动员与否,GVHD发生程度差异有统计学意义。(2)2∶1及1∶1混合骨髓移植(MBMT)组小鼠有中到重度GVHD表现;经G CSF动员的MBMT组小鼠8周存活率较未动员组明显提高(P<0.05)。(3)G CSF动员供鼠后L3T4+细胞下降显著,L3T4+/Lyt2+比值明显低于未动员组(P<0.01)。(4)G CSF动员供鼠后混合淋巴细胞反应(MLR)细胞培养上清中,IL 2、IFN γ水平降低,IL 4 水平升高。结论 同基因骨髓混合一定量 H 2半相合异基因骨髓移植可减轻GVHD的发生;G CSF动员供鼠可进? Objective To explore whether acute graft versus host disease (aGVHD) could be alleviated by syngeneic bone marrow mixed with granulocyte colony stimulating factor (G CSF) mobilized H 2 haploidentical marrow grafting. Methods Female BALB/c and neonatal BALB/c mice were recipients and male (BALB/c×C 57 BL/6) F 1 (BCF 1) mice were donor mice respectively. Donor mice were injected subcutaneously with G CSF daily at 0.01 μg/g body weight or saline for 6 days, and splenocytes were harvested on day 6. Spleen index(SI) represented GVHD in neonatal mice after the intraperitoneal injection of mixed spleen cells.Lethally irradiated ( 60 Co, 8.5 Gy) adult mice were transplanted with a mixture of syngenetic plus G CSF mobilized (control diluents) H 2 haploidentical marrow cells.Survival time and survival rate of the recipients were observed after mixed marrow transplantation (MBMT). GVHD was assessed by observing signs of weight loss, ruffled fur, diarrhea and histological change of skin, liver and small intestines. Enzyme linked immunosorbemt assay (ELISA) method was used to detect cytokines (IL 2, IL 4, IFN γ). Fluorescence activated cell sorting (FACS) analysis was used to detect T cell phenotype. Results (1) The neonatal mice subject to injection of 2∶1 and 1∶1 mixed spleen cells and H 2 haploidentical spleen cells all suffered from aGVHD. The severity of aGVHD in recipient mice receiving G CSF mobilized splenocytes was dramatically reduced. (2) The aGVHD signs and histological change were observed in most mice of 2∶1 and 1∶1 MBMT groups. However, the survival time of G CSF mobilized MBMT groups was longer than in control groups ( P < 0.05 ) and these mice had signs of moderate GVHD. (3) The Absolute number of Thy1.2 + and lyt2 + cells was decreased and relative ratio in both subsets was significantly reduced in G CSF treated donor mice. (4) The supernatants from a primary MLR were collected at 48 h for cytokine measurement. The results showed an increas
出处 《中华器官移植杂志》 CAS CSCD 北大核心 2005年第2期87-90,共4页 Chinese Journal of Organ Transplantation
关键词 粒细胞集落刺激因子 小鼠 骨髓移植 移植物抗宿主病 实验研究 Granulocyte colony-stimulating factor Graft-versus-host disease Bone marrow transplantation Mouse
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参考文献7

  • 1孟玉茹,黄平.淋巴因子激活的骨髓细胞或脾细胞对小鼠移植物抗宿主病的预…[J].中华血液学杂志,1993,14(11):564-566. 被引量:3
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二级参考文献5

  • 1孟玉茹,国外医学输血及血液学分册,1992年,6卷,334页 被引量:1
  • 2何晓,上海免疫学杂志,1985年,5卷,331页 被引量:1
  • 3孟玉茹,国外医学输血及血液学分册,1992年,6卷,334页 被引量:1
  • 4杨骏,中华器官移植杂志,1991年,12卷,35页 被引量:1
  • 5何晓,上海免疫学杂志,1985年,5卷,331页 被引量:1

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