中文摘要：

目的探讨神经干细胞和多巴胺神经元联合移植改善帕金森病大鼠运动障碍的效果。方法采用经典6-羟基多巴胺毁损法构建帕金森病大鼠模型36只,腹腔注射阿朴吗啡连续诱导4周。APO注射第4周将36只帕金森病大鼠随机分为对照组、多巴胺组、干细胞组及联合组,每组9只,分别于右侧纹状体区立体定向注入生理盐水、多巴胺神经元悬液、神经干细胞悬液、多巴胺神经元与神经干细胞悬液。计算各组移植后2、4、6、8周的旋转次数;干细胞组及联合组分别于移植后1、2、4、8周行MRI扫描,观察移植区影像学变化;移植后8周取各组脑组织行普鲁士蓝染色,观察移植细胞定植与迁移情况,免疫荧光法检测移植细胞分化情况。结果移植后2、4、6、8周,对照组、神经干细胞组、多巴胺组、联合组旋转次数依次降低,组间两两比较P均〈0.01。MRI检查结果：随着时间延长,联合组与干细胞组移植区T2 W/FFE成像上呈低信号影的区域逐渐变大,但联合组低信号影范围大于干细胞组。普鲁士蓝染色结果：干细胞组和联合组移植的神经干细胞及其分化后的细胞胞质内均可见大量蓝色颗粒,大部分存留在移植针孔附近,仅少部分细胞向远处迁移,但联合组蓝色颗粒数量以及扩散范围均大于干细胞组。联合组巢蛋白（Nestin）、酪氨酸羟化酶（TH）、绿色荧光蛋白（GFP）阳性细胞数及Nestin/GFP、TH/GFP均高于干细胞组,酸性纤维蛋白（GFAP）阳性细胞数及GFAP/GFP均低于干细胞组（P均〈0.01）。结论神经干细胞与多巴胺神经元联合移植可显著改善帕金森病大鼠的运动障碍,更有助于神经干细胞的定植、迁移及分化成为多巴胺神经元。

英文摘要：

Objective To explore the efficacy of combined transplantation of neural stem cells （NSCs） and dopaminergic （DA） neurons in treatment of dyskinesia in rats with Parkinson disease （PD）. Methods Thirty-six rat models with PD were established by using the classical 6-hydrodopamine damage protocol, and followed by 4-week rotation induction via apomorphine （APO） intraperitoneal injection. These 36 PD rats were randomly divided into the following groups after 4 weeks of APO intraperitoneal injection： the control group, the DA neurons group, the NSCs group, and the NSCs-DA group, and normal saline （NS）, CM-DiI labeled DA neurons, GFP-SPIO double labeled NSCs, and CM-Dil labeled DA neurons combined with double labeled NSCs neurons were transplanted into the right striatum of these groups by stereotactic injection, respectively. The rotation frequency of these groups was calculated at week 2, 4, 6, and 8 after the transplantation. Moreover, the NSCs group and DA-NSCs group were scanned by MRI at week 1, 2, 4, and 8. The brain tissues of these groups were collected to observe the migration and homing of the transplanted cells after 8 weeks through prussian blue staining, and the differentiation of NSCs was measured by immunofluorescence. Results The rotation frequencies of the control group, the DA neurons group, the NSCs group, and the NSCs-DA group were decreased gradually, and significant difference was found between every two groups, all P 〈 0.01. The results of MRI scan between NSCs group and NSCs-DA group were as following ： over the time of transplantation, the hypointense signal area in T2 W/FFE imaging of both groups were larger than before, and the area in the NSCs-DA group was larger than that of the NSCs group. The results of prussian blue staining suggested that there were a lot of blue particles in the cytoplasm of NSCs and its differentiated cells, which were grafted from the NSCs group and NSCs-DA group. However, just a few cells migrated from the transplantation needle core to the