环磷酰胺对小鼠骨髓造血干/祖细胞作用及机制研究

目的探讨环磷酰胺(CY)对小鼠骨髓造血干/祖细胞损伤的作用特点与机制。方法分别以大(380mg/kg)、中(200mg/kg)、小(100mg/kg)三种剂量CY腹腔注射BALB/C小鼠,注射后一周内动态检测外周血白细胞(WBC)、骨髓及外周血CD34+细胞含量、骨髓有核细胞数(NC)与细胞凋亡及病理学改变。结果①在CY处理后3～4d内,骨髓病理损伤逐渐加重,外周血WBC和骨髓NC逐渐下降直至最低值,受抑程度与CY剂量呈显著正相关。②外周血CD34+细胞与骨髓CD34+细胞水平变化基本一致,均在CY注射后1～3d进行性降低,随后中、小剂量组先一过性迅速上升至高出正常水平,然后再下降,而大剂量组则一直处于缓慢回升。③CY处理后1～3d内骨髓细胞凋亡明显增加。结论CY短期内对小鼠造血干/祖细胞损伤存在剂量—时间效应关系,中、小剂量起“动员”作用,大剂量起“摧毁”作用,诱导细胞凋亡是造血损伤的机制之一。

Effect of cyclophosphamide on murine bone marrow hematopoietic stem/progenitor cells and its mechanism

Objective To investigate the changes of bone marrow hematopoietic stem /progenitor cells and its mechanism after cyclophosphamide(CY)treatment in mice.Methods BALB/C mice were given a single intraperitoneal injection with three dosages of CY 100 mg/kg(low-dosage group),200 mg/kg(middle-dosage group)and 380 mg/kg(large-dosage group)body weight respectively.The dysfunction of hematopoiesis,apoptosis of bone marrow cells,distribution of CD34+ hematopoietic stem/progenitor cells and bone marrow pathology were all examined during a week after administration.Results ①Within 3~4 days after CY treatment significant dosage-time effect of CY-injured hematopoesis was observed,and the peripheral WBC and bone marrow nuclear cells decreased to the lowest level.②The changes of CD34+ cells in peripheral blood matched those of bone marrow.Compared with normal group,the number of CD34+ cells decreased at first in all dosage groups,then increased and exceeded the pre-treatment level at day 5,and then decreased in low-and middle-dosage group.However in large-dosage group,that was significantly lower at the detection time.③Apoptosis rate of bone marrow cells increased within 1~3 days after CY treatment.Conclusion There were significant dosage-time effects of CY-injured hematopoesis in mice.Low-dosage and middle-dosage of CY play a role of mobilization,while large-dosage of destruction and inducing apoptosis may be one of important mechanisms for that.