低剂量照射治疗免疫介导性再生障碍性贫血实验探究.docVIP

低剂量照射治疗免疫介导性再生障碍性贫血实验探究 　 作者：刘洪涛,赵钧铭,褚建新 【摘要】 　　免疫介导性再生障碍性贫血（immunomediated aplastic anemia, IMAA）时淋巴细胞处于激活状态，被抑制的造血干细胞处于静止状态，据此本研究探讨一项新的治疗IMAA的策略，即利用激活的淋巴细胞和静止的造血干细胞对放射敏感性的差异，给IMAA小鼠低剂量全身照射，此低剂量照射既可杀灭免疫活性淋巴细胞，解除它对造血干细胞的抑制，又不损害造血干细胞，从而使造血得以恢复。实验应用免疫介导性再生障碍性贫血小鼠模型完成，于造模后第4天全身照射150 cGy，以不治疗照射组和单纯照射组小鼠为对照，观察各组小鼠生存时间和生存率、血象和骨髓有核细胞数、骨髓和淋巴组织的病理形态改变。结果表明：　 ①IMAA组小鼠活存率为12.5%，平均存活时间为27.4±13.4天，照射治疗组活存率为100%，平均存活时间60天以上，单纯照射组无死亡；②外周血白细胞数： IMAA组呈进行性下降，直至死亡，照射治疗组第10天与免疫再障组相似，以后开始缓慢回升，基本上达到治疗前水平；　③红细胞比容：未治疗IMAA组于14天后呈进行性降低, 至第35天比实验前减低2/3，照射治疗组与单纯照射组一样，第14天有轻度减低随后升高，至35天接近正常；　④骨髓有核细胞数： IMAA组呈进行性减低，无恢复趋势，照射治疗组于一过性减低后迅速增加，第28天达到正常水平；　⑤骨髓和淋巴组织病理形态观察： IMAA组小鼠呈典型再生障碍性贫血病理改变，骨髓造血衰竭，脾脏明显萎缩，而照射治疗组于第28天骨髓和脾淋巴脏组织基本上恢复正常。　结论：低剂量全身照射对IMAA小鼠有明显的治疗作用，骨髓和淋巴组织完全恢复；其疗效机制可能与低剂量照射杀灭免疫活性淋巴细胞解除了对造血干细胞的抑制有关。本研究结果不仅为免疫介导性再生障碍性贫血提出了一种新的治疗对策，而且为免疫介导性再生障碍性贫血机制的研究提供了新线索，在文献中尚未见有类似报道。 【关键词】 低剂量照射　免疫介导性再生障碍性贫血 小鼠　免疫活性细胞 　　Experimental Study of Low Dose Irradiation for Treatment of ImmunoMediated Aplastic Anemia in Mice Abstract As the lymphocytes of immunomediated aplastic anemia (IMAA) are in active state, and the hematopoietic stem cells are in silence, this study was aimed to design a new strategy to treat IMAA. To utilize the difference of radiosensitivity between active lymphocytes and silent hematopoietic stem cells, the animals suffered from IMAA were treated with a single low dose of irradiation, killing the active lymphocytes to release its suppression to hematopoietic stem cells without injuring the hematopoietic stem cells. Therefore, the hematopoiesis can be restored. Experiments were completed in IMAA mouse model. At day 4 after making IMAA, the model mice were giren total body irradiation of 150 cGy, the nontreated model mice and normal mice irradiated with 150 cGy were used as control. The survive time and survive rate of mice, blood picture, the account of nucleated cell of bone marrow, and pathological changes of bone marrow and lymphoid tissues of each group mice were observed. The r