非清髓性干细胞移植治疗狼疮鼠

Treatment of BXSB with Nonablative Stem Cell Transplantation

【目的】探索用非清髓性干细胞移植治疗BXSB狼疮鼠的有效性及安全性。【方法】实验组用氟哒拉宾、环磷酰胺作预处理 ,对照组用马利兰 +环磷酰胺作预处理 ,动态观察两组外周血细胞变化 ,流式细胞仪检测移植后受者CD3 -CD5+ 、CD3 + CD5+ 的改变 ,聚合酶链反应 短串联重复序列分析移植后BXSB鼠嵌合状态 ,免疫荧光法检测移植前后受者的肾病理变化。【结果】实验组白细胞、血小板、血红蛋白下降最低值分别为 (0 6± 0 2 )× 10 9/L、(2 7 0± 7 6 )× 10 9/L、(48 0± 1 2 ) g/L ,均分别高于对照组 (P 均 <0 0 5 ) ,白细胞上升至 1 0× 10 9/L的时间在实验组为 (17 5± 6 3)d ,比对照组明显缩短 (P <0 0 5 ) ,尿蛋白减少、抗ds DNA抗体转阴、肾免疫荧光减少在两组间差别无显著性 (P均 >0 0 5 ) ,移植后 8周实验组CD3 -CD5+ 、CD3 + CD5+ 开始上升 ,出血、体质量下降、肺部感染发生率、死亡率实验组明显低于对照组 (P均 <0 0 5 ) ,移植 30d后实验组DNA指纹图提示为混合嵌合体。【结论】非清髓性干细胞移植可有效改善BXSB鼠狼疮表现 ,该方法抑制骨髓的功能较弱 ,造血恢复较快 ,与移植相关的并发症、死亡率发生率低 ,是一种较安全。

To investigate the effectiveness and safety of nonablative stem cell transplantation(NST) on the treatment of BXSB lupus mice. The experimental group (group of NST) was pretreated with fludarabine and cyclophosphamide, while the control group (Allo SCT) was pretreated with myleran and cyclophosphamide. Peripheral blood cells were observed, CD 3 -CD 5 + and CD 3 +CD 5 + of recipients were measured by flowcytometry. Recipients' mixed chimerism were analyzed with polymerase chain reaction short tandem repeat and recipients'kindey pathological changes were examined with direct immunofluorescence after transplantation. The lowest values of WBC, PLT and Hb fall in the NST group were (0 6±0 2)×10 9/L, (27 0±7 6)×10 9/L and (48 0±1 2) g/L, respectively. They were all higher than those of the control group(P all < 0 05).The time for WBC rising from the lowest value to 1 0×10 9/L were 17 5±6 3 days in the NST group, which was shorter than that in the control group(P<0 05). There were no statistically significant difference in the reduction of urinary excretion of proteins, change of anti d sDNA and reduction of kindey immunofluorescence between the two groups(P all >0 05). Early immune reconstitution began to recover 8 weeks after transplantion in the NST group. The incidences of bleeding, loss of body weight, penumonia and mortality related to transplantation were lower in the NST group than those in the control group (P all<0 05). Recipients' mixed chimerism in the NST group appeared 30 days after transplantation. [Conclusion] NST can improve all manifestations of lupus mice effectively. NST show less suppression to bone marrow function. Hematopoietic function recovers faster with NST than with Allo SCT. Incidences of complications and mortality related to transplantation in the NST group are lower than that in the Allo SCT group. NST is a safe and effective method for the treatment of lupus mice.