人脐带血间充质干细胞和神经干细胞移植对帕金森模型大鼠神经营养作用的比较

Neurotrophic effects of human umbilical cord blood derived mesenchymal stem cells and neural stem cells transplantation on rats with Parkinson's disease

目的:比较人脐带血间充质干细胞(hUCB-MSCs)和中脑神经干细胞(NSCs)移植治疗帕金森病大鼠的神经营养作用。方法:6-羟基多巴胺所致偏侧帕金森病SD大鼠模型随机分为3组,分别为中脑NSCs组、hUCB-MSCs组、生理盐水组。造模成功后3周,将磷酸缓冲液(PBS)和溴尿嘧啶(BrdU)标记的NSCs及hUCB-MSCs立体定向注入模型鼠右侧纹状体,检测大鼠旋转行为。在移植后8周对3组大鼠进行Morris水迷宫实验,并对大鼠脑纹状体区进行免疫组织化学显色检测纹状体移植区脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)表达的变化。结果:移植4、8周后,NSCs组、hUCB-MSCs组大鼠的旋转次数比生理盐水组均减少。移植8周后,水迷宫实验显示NSCs组和hUCB-MSCs组第1~5天平均潜伏期均短于生理盐水组,NSCs组、hUCB-MSCs组穿越平台次数均高于生理盐水组。但在大鼠旋转次数和水迷宫实验中,NSCs组和hUCB-MSCs组之间均无统计学差异。移植治疗8周后,纹状体移植区NSCs组、hUCB-MSCs组的BDNF和GDNF表达较生理盐水组显著增多;hUCB-MSCs组的BDNF和GDNF表达较NSCs组增多更明显。结论:NSCs、BMSCs的移植明显增加帕金森病大鼠纹状体移植区BDNF、GDNF的表达水平,并改善大鼠运动及认知功能;hUCB-MSCs移植在纹状体移植区BDNF、GDNF表达水平多于NSCs移植组,hUCB-MSCs神经营养效应可能更强,更适合应用于临床治疗。

Objective： To compare the neurotrophic effect of human umbilical cord blood derived mesenchymal stem cells （hUCB-MSCs） and neural stem cells （NSCs） transplantation on rats with Parkinson＇s disease. Methods： Fifty-eight SD rats with 6-OHDA-induced Parkinson＇s disease （PD） on the right side were randomly divided into NSCs group, hUCB-MSCs group and saline group, respectively. Three weeks after the modeling, bromo-uracil （BrdU） labeled NSCs, hUCB-MSCs, saline saline were injected into the right striatum of rat model to detect the rotation of rats in the above three groups. At week 8, the expression of brain derived neurotrophic factor （BDNF） and glial cell line, derived neurotrophic factor （GDNF） in three groups after transplantation was tested in the brain striatum by immunohistochemical staining. Results： The number of rotation in NSCs and hUCPrMSCs group was sharply decreased in comparison with those in saline group. In place navigation test, rats in NSCs and hUCPrMSCs group had shorter latency compared with saline group at week 8 after transplantation. In spatial probe test, rats in NSCs and hUCB-MSCs group swam more times in platform quadrant than those in saline group. But there was no statistical difference between the NSCs group and the hUCB-MSCs group in the number of rotation and water maze test. At week 8, the expression of BDNF, GDNF in NSCs and hUCB-MSCs group after transplantation increased significantly than that in the control group. The values of BDNF and GDNF in hUCB-MSCs group at week 8 were sharply increased in comparison with those in NSCs group after transplantation. Conctusion： The transplantation of NSCs and hUCB-MSCs significantly increases the expression of BDNF and GDNF in the striatum of PD rats and improves the movement and cognitive function of PD rats. The levels of BDNF and GDNF in hUCB-MSCs group after transplantation are observably higher than those in NSCs group, which suggests that the neurotrophic effect of hUC-MSCs may be stronger than those of NSCs, so hUCB-MSCs is more suitable for clinical treatment.