环磷酰胺对小鼠骨髓造血干/祖细胞作用及机制研究  

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

作　　者：徐宏贵[1] 方建培[1] 黄绍良[1] 魏菁[2] 吴燕峰[1] 包蓉[1] 

机构地区：[1]中山大学附属第二医院儿科,广州510120 [2]中山大学附属第二医院医研中心,广州510120

出　　处：《中国小儿血液与肿瘤杂志》2007年第3期106-110,共5页Journal of China Pediatric Blood and Cancer

摘　　要：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。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 pretreatment 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.

关 键 词：环磷酰胺 造血干/祖细胞 凋亡 小鼠 

分 类 号：R96[医药卫生—药理学]