表达绿荧光蛋白的多药耐药微小残留白血病细胞的小鼠模型

Establishment of A Mouse Model for Detecting Multi-drug Resistant Minimal Residual Leukemia Cells Expressing Green Fluorescent Protein

为了方便研究多药耐药微小残留白血病的病理生理和治疗,采用携带绿荧光蛋白(EGFP)基因标记的小鼠多药耐药白血病细胞系P388/VCRG和DBA小鼠建立一个检测多药耐药微小残留白血病的动物模型。结果显示,P388/VCRG细胞腹腔接种DBA小鼠,白血病的发病率为100%,无自发缓解。P388/VCRG白血病模型小鼠对环磷酰胺(Cy)敏感,有较好的药物剂量生存时间关系,接种细胞的对数与Cy剂量间有良好回归相关关系。白血病诱导缓解后残留白血病细胞在肝、脾、胸腺及骨髓等脏器呈不均匀分布。冰冻切片荧光显微镜下观察EGFP+细胞是检测小鼠体内微小残留白血病细胞最敏感的方法。结论:采用P388/VCRG细胞和DBA小鼠可建立表达EGFP的多药耐药小鼠微小残留白血病模型。

This study aimed to investigate the pathophysiology and therapy of multi-drug resistant model of minimal residual leukemia in mice, The multi-drug resistant model of minimal residual leukemia was established by using P388/ VCR-G cell line expressing enhanced green flourescent protein （EGFP） and DBA mice. The results showed that P388/ VCR-G were inoculated in the abdominal cavities of DBA mice, the incidence of leukemia was 100%. Any of these mice with leukemia could not obtain remission spontaneously, The model of leukemia was sensitive to cyclophosphamide （Cy） and the time of survial was related to the dose of Cy received. The logarithm of cells inoculated in mice correlated regressionally with the dose of Cy. So this model was ideal for reseach on minimal residual leukemia. The distribution of residual leukemia cells in complete remission was not uniform in different organs including liver, spleen, thymus and bone marrow. Minimal residual leukemia cells could be found by flourescent microscopy in freezing tissue slice. It is concluded that the multi-drug resistant model of minimal residual leukemia expressing EGFP can be established by using P388/VCR-G cell line and DBA mice. The minimal residual leukemia cells can be observed by fluorescence microscopy in complete remission stage.