神经细胞移植对帕金森病大鼠模型的治疗作用观察

Effects of neural cells transplantation on rat model of Parkinson's disease

目的比较胚胎多巴胺神经元、未经诱导和诱导的中脑来源的神经干细胞移植治疗帕金森病（PD）的疗效。方法将40只SDPD大鼠随机均分为4组，每组10只，分别在纹状体内植入未经诱导的中脑来源的神经干细胞（B组）、胚胎多巴胺神经元（C组）和经诱导的中脑来源的神经干细胞（D组），对照组（A组）仅在纹状体内注入生理盐水，观察移植后2、4、8周各组大鼠旋转行为改善情况，并采用酪氨酸羟化酶（TH）免疫组化染色比较各组大鼠脑内存活TH阳性神经元的数量。结果A组移植前后各时间点旋转次数无明显差异（F=0．294，P=0．830）。B组移植后旋转次数有所减少，但差异无统计学意义（F=0．335，P=0．800）。C组和D组移植后4～8周时旋转次数均明显减少（分别为F=26．838，p=0．000；F=14．571，p=0．000），但两组之间比较无明显差异（p=0．764）。TH免疫组化染色显示，A组未见TH阳性细胞，B组可见少量TH阳性细胞（共80±36个），C组移植后存活的TH阳性细胞数共679±286个，而D组共665±264个，后两组之间比较无明显差异（P：0．548）。结论胚胎多巴胺神经元和经诱导的中脑来源的神经干细胞移植可有效的改善PD大鼠的旋转行为。

Objective To investigate the therapeutic effects of embryonic dopaminergic neurons, mesencephalon derived neural stem cells with or without pre differentiation as grafts in the treatment of Parkinson＇s disease （PD） in SD rats. Methods Forty SD Parkinsonian rats were randomly assigned to four groups as follows： normal saline grafted group （A）, mesencephalon-derived neural stem cells without pre-differentiation grafted group （B）, embryonic dopaminergic neurons grafted group （C） and mesencephalon-derived neural stem cells with pre-differentiation grafted group （D）. Normal saline and different cells were transplanted into the rat＇s striatum by stereotactic technique. Therapeutic effects were evaluated based on the improvement of rat＇s rotation behavior at 2nd, 4th and 8th week after operation and survival of tyrosine hydroxylase （TH） immunoreactive （TH-ir） cells at 8th week after operation. Results No obvious amelioration in number of rotation was found in group A （F=0. 294, P=0. 830）. In group B, the number of rotation was decreased after operation, but the differ ence was not significant compared with that before operation （F=0. 335, P=0. 800）. The numbers of rotation were obviously decreased in group C （F=26. 838, P=0. 000） and group D （F=14. 571, P=0. 000） at 8tb week after operation, but no significant difference was found between the two groups （P=0. 764）. TH immunohistochemical staining showed that the number of TH positive cells was 665±264 in group D, 679±286 in group C, 80±36 in group B, and 0 in group A, and no significant difference existed between group C and D （P=0. 548）. Conclusion As grafts, both embryonic dopaminergic neurons and mcscncephalo-derived neural stem cells with prc-differentia tion can improve the rotational behavior and cellular morphology of Parkinsonian rats after neural cells transplantation.