骨髓干细胞移植治疗对肝豆状核变性早期TX小鼠脑肾铜代谢的影响

Marrow Stem Cell Transplantation on Brain and Kidney of Early Stage of Wilson's Disease in TX Mice

[目的]探讨骨髓干细胞移植对于疾病早期肝豆状核变性模型鼠—TX小鼠脑、肾组织铜代谢的影响.[方法]4～5周龄的雄性DL小鼠50只为供体;2月龄的TX小鼠50只为受体（雌∶雄=3∶2）,随机分为移植组和对照组各25只（雌∶雄=3∶2）.分离供体小鼠骨髓干细胞并标记CM-DiI荧光,经尾静脉注入移植组TX小鼠体内,每只小鼠0.2 mL（1.2×107个细胞）,对照组动物注入等量平衡盐液体.移植后的1、2、4、8、12周处死动物检测脑、肾铜含量情况,并以CM-DiI荧光示踪技术考察干细胞在受体鼠脑、肾组织的分布情况.[结果]移植治疗后脑和肾脏铜含量（脑铜平均28.7 mg/kg,肾铜平均31.7mg/kg）较对照组（脑铜平均34.5 mg/kg,肾铜平均36.9 mg/kg）均有下降趋势,达到对照组铜含量的70％～98％;移植后第4周时治疗组脑铜含量（28.4±5.5） mg/kg,仅为对照组（40.1±6.9） mg/kg的70％,改变有统计学意义（P＜0.05）.示踪研究在移植后各时间点均可于脑内检测到供体细胞,肾脏未检测到供体细胞.[结论]疾病早期TX小鼠接受骨髓干细胞移植治疗,对脑内铜代谢有一定改善作用,对肾脏铜代谢无明显改善作用.

[ Objective ]To explore the effects of unsorted bone marrow stem cells transplantation on the brain and kidney of TX （toxic milk） mice at early stage （2-month-old） of Wilson disease. [ Methods ] 50 male 4-5-week-old DL mice were enrolled as donator. 50 2-month-old TX mice as recipient （F：M = 3：2） were grouped to transplantation and control group with 25 mice in eacb group （F ： M = 3 ： 2）. Bone marrow stem cells （BMSC） were harvested from donor DL mice by the whole bone marrow method in vitro, labeled with CM-DiI, then sterilely injected into receptor mice via the caudal vein, 0.2 mL （1.2 ~ 107 cells） per mouse. At week 1, 2,4,8,and 12 post transplantation, copper concentration of brain and kidney were studied to compare the effect of transplantation therapy. CM-DiI fluorescence were studied for tracing study of the donor ceils. [ Results ] Brain and kidney copper concentration of the transplanted group （average brain copper concentration： 28.7 mg/kg, average kidney copper concentration： 31.7 mg/kg） reduced to 70% - 98% of the control group （average brain copper concentration： 34.5 mg/kg, average kidney copper concentration： 36.9 mg/ kg）. Brain copper concentration of the recipient mice decreased to 28.4±5.5 mg/kg at the 4th week post transplantation, which was 70% concentration of the control group （40.1±6.9 mg/kg, P 〈 0.05）. The donor cells with CM-DiI fluorescence could be tracked in the recipient brain at all the time points but never in the kidney. [Conclusion] For the early stage TX mice, bone marrow stem cells transplantation wins some curative effect on brain copper concentration, but no positive results were got from the kidney.