帕金森病大鼠模型定向移植Resovist标记骨髓基质干细胞的活体MR示踪

In vivo MR tracking of transplanted bone marrow stromal cells labeled with Resovist in rat models with Parkinson disease

目的筛选并确定特定条件下行帕金森病（PD）大鼠模型纹状体定向移植骨髓基质干细胞（BMSCs）磁共振（MR）活体观察的最佳移植细胞数量及最佳观察时间。方法40只PD大鼠分为5组,移植Resovist标记BMSCs数量分别为1×105（第1组）、1.5×105（第2组）、2×105（第3组）、2.5×105（第4组）和对照组（第5组,注射生理盐水）,每组8只。运用FFE-T2WI序列在移植前、移植后1、4、8周对其行MR检查和阿朴吗啡旋转试验,测量并比较各组大鼠在各观察时间点脑内低信号区的体积大小,评估不同数量移植细胞的迁移情况,并观察其对PD大鼠的行为学治疗效果。移植细胞后12周,MR检查后处死大鼠行免疫组化检查。结果第1和第2组随时间延长MRI低信号区体积变小;第3和第4组第4周的低信号区体积大于第1周,但仅第3组差异有统计学意义（P=0.005）;第3组每分钟旋转次数降低幅度最大,与对照组差异有统计学意义（P=0.02）。结论与行为学试验相对应,2.0×105剂量组可作为活体MR观察的最佳剂量;立体定向移植BMSCs后1-4周可作为MR活体观察最佳时间。

Objective To observe the migration ability of different quantity of BMSCs labled with Resovist after transplanted in rat models with Parkinson disease（PD） with 1.5T MR scanner and micro-47 coil,in order to determine the optimal transplanted dosage of BMSCs and observation time in vivo.Methods Forty PD rats were randomly assigned to 5 groups（each n=8） including 1×105 BMSCs group,1.5×105 BMSCs group,2×105 BMSCs group,2.5×105 BMSCs group and control group.FFE-T2WI were obtained immediately and 1 week,4 weeks,8 weeks after transplantation to measure and compare the volume of hypointense areas of different groups in different time with 1.5T and 47 mm inner diameter micro-coil.At the meantime,rotational behavior was assessed in each group.After MR scanning,the rats were executed and prepared for immunohistochemistry staining at 12 weeks after transplantation.Results Only the extent of the dark region became wider 4 weeks after transplantation in 2×105 BMSCs group（P=0.005）.The therapeutic efficacy in 2×105 BMSCs group was the best confirmed by behaviour studies（P=0.02）.Conclusion For the treatment of PD and evaluation of the migratory ability of BMSCs,the optimal transplanted dosage of BMSCs is 2×105,while the best observation time is 4 weeks after transplantation.