多药耐药基因在骨髓移植模型中的表达

Expression of mdr1 gene in a murine bone marrow transplantation model

目的 探讨多药耐药基因 (mdr1)在骨髓移植小鼠模型中表达情况 ,及转染mdr1的骨髓细胞对化疗中骨髓保护的可行性。方法 以小鼠骨髓细胞为靶细胞 ,通过逆转录病毒介导 ,将mdr1转入骨髓细胞。通过将转染基因的骨髓细胞回输同种小鼠体内的骨髓移植动物模型 ,观察不同时期移植小鼠骨髓细胞中mdr1的表达及功能。结果 ①成功地将mdr1导入小鼠骨髓细胞中 ,转染率达到35 % ;②采用程序性移植方法成功建立了mdr1转基因鼠骨髓移植模型 ;③mdr1在移植小鼠细胞内稳定、有效地表达 ,观察 1～ 5个月mdr1转染的细胞在受体鼠骨髓单个核细胞中所占比例分别为 8.0 % ,8.0 % ,7.5 % ,4 .0 % ,3.0 % ;④mdr1转染的骨髓细胞在化疗中有明显的骨髓保护作用。结论 从一个侧面证实了通过mdr1转染骨髓细胞在化疗中进行骨髓保护是一种长期、稳定、有效的方法。

Objective To investigate the expression of mdr1 gene in hematopoietic cells of a murine bone marrow transplantation model and to explore the feasibility of transferring mdr1 gene into hematopoietic cells to pro vent myelosuppression from chemotherapy. Methods mdr1 gene was transferred into hematopoietic cells of murine bone marrow by retrovirus vector. The expression and function of mdr1 gene in vivo was tested in a murine bone marrow transplantation model. Results ①mdr1 gene was successfully transferred into murine MNC, the transduction rate was 35%. ②mdr1 gene transferred murine bone marrow transplantation model was established successfully by scheduled bone marrow transplantation method. ③In 1～5 months period, stable and effective expression of mdr1 gene could be detected in hematopoietic cells of the recipient mouse, the percentage of mdr1 gene expression cells in recipient's hematopoietic cells decreased monthly to 8.0%,8.0%,7.5%,4.0% and 3.0%. ④mdr1 expression hematopoietic cells had efficient resistance to chemotherapy. Conclusion It is an effective approach to transfer mdr1 gene into hematopoietic cells for proventing myelosuppression in chemotherapy.