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【目的】建立环磷酰胺 (CTX)预处理脐血移植 (UCBT)小鼠模型 ,并探讨预处理后骨髓龛位腾出的特点和机制。【方法】分别以 10 0 ,2 0 0 ,380mg/kg 3种剂量CTX腹腔注射BALB/c小鼠 ,检测注射后 1周内外周血象、骨髓及外周血CD34+细胞含量、骨髓细胞凋亡及病理学改变。用C5 7BL/ 6鼠脐血 (FNPB)作供体移植经“致死量”CTX预处理的BALB/c鼠 ,动态观察移植后受鼠存活状况、植入水平、造血与免疫功能恢复及移植物抗宿主病 (GVHD)情况。【结果】在CTX处理后 3~ 4d内 ,骨髓造血细胞损伤渐加重 ,血窦结构紊乱 ,细胞碎屑弥漫分布 ,外周血与骨髓CD34+ 细胞水平进行性降低至最低值 ,下降的速度和程度与CTX剂量呈正比。骨髓细胞凋亡发生率的峰值出现在第 1天 ,第 3天恢复正常。FNPB移植能明显提高受鼠存活率 ,重建部分造血与免疫功能 ,未见明显GVHD表现 ,并在受体内检出供体细胞的植入。【结论】成功建立CTX化疗预处理小鼠脐血移植模型。干细胞占据的龛位是在化疗预处理后 4d逐渐完成腾空 ,凋亡是参与此过程的机制之一。
【Objective】 To establish a mouse model of cord blood transplantation (UCBT) treated with cyclophosphamide (CTX) and to explore the characteristics and mechanism of bone marrow niche vacancy after pretreatment. 【Methods】 BALB / c mice were injected intraperitoneally with CTX at dose of 10 0, 200, 380 mg / kg respectively, and the levels of CD34 + cells in peripheral blood, bone marrow and peripheral blood, apoptosis of bone marrow cells and bone marrow Neo-Confucianism changes. BALB / c mice pretreated with “lethal dose” CTX were transplanted with C5 7BL / 6 murine cord blood (FNPB). The survival, engraftment, hematopoietic and immune function recovery and graft Anti-host disease (GVHD) situation. 【Results】 Within 3 to 4 days after CTX treatment, bone marrow hematopoietic cell injury gradually aggravated, sinusoidal structure was disorganized, cell debris diffuse distribution, peripheral blood and bone marrow CD34 + cells were progressively reduced to the lowest level, and the rate and degree of descent CTX dose is proportional. The peak of the incidence of bone marrow cell apoptosis occurred on the first day and returned to normal on the third day. FNPB transplantation can significantly improve the survival rate of mice, reconstruction of some hematopoietic and immune function, no significant GVHD performance, and in the recipient donor cells were detected. 【Conclusion】 CTX chemotherapy was successfully established in cord blood transplantation in mice. The niche occupied by stem cells was gradually emptied 4 days after chemotherapy pretreatment. Apoptosis is one of the mechanisms involved in this process.