【摘要】 为比较大鼠胚胎大脑皮质和中脑神经干细胞(NSCs)移植入Parkinson病(PD)模型鼠后动物行为的改善和植入细胞分化为酪氨酸羟化酶(TH)阳性神经元的情况,本研究将大鼠胚胎大脑皮质和中脑NSCs在体外分离、扩增、BrdU标记后,添加或不加白细胞介素-1α(IL-1α)、白细胞介素-11(IL-11)、白血病抑制因子(LIF)和胶质细胞源性神经营养因子(GDNF)等因子,分别移植入PD模型鼠病侧纹状体中。术后每隔2周进行动物旋转行为的检测,第12周时用免疫荧光双重标记方法检测BrdU和TH双标神经元。结果显示:中脑NSCs+因子移植组,动物的旋转行为得到明显改善;单纯中脑NSCs移植组次之;而单纯皮质NSCs移植组、皮质NSCs+因子移植组及生理盐水对照组动物的行为无明显改善。免疫荧光双重染色结果显示,中脑NSCs+因子组和单纯中脑NSCs组BrdU和TH双标神经元的数量明显多于其它组,而中脑NSCs+因子组又多于单纯中脑NSCs组。以上结果提示,大鼠胚胎中脑NSCs移植治疗PD模型的疗效明显优于胚胎皮质NSCs,IL-1α、IL-11、LIF和GDNF等因子能促进移植的中脑NSCs分化为TH阳性神经元。更多还原

【Abstract】 To compare the behavior improvement of Parkinson’s disease(PD) model rats and differentiation into TH positive neurons after grafting of stem cells, the cortical and mesencephalic neural stem cells (NSCs) were separately isolated, proliferated and labeled with 5-bromo-2’- deoxyuridine (BrdU) in vitro from fetal rats. After adding or without adding some cytokines such as interleukin-1α (IL-1α), interleukin-11 (IL-11), leukemia inhibitory factor (LIF) and glial cell derived neurotrophic factor (GDNF), these NSCs were transplanted into the lesioned striatum of PD model rats. The rotation behavior of rats was observed every 2 weeks after transplantation until these rats were killed after 12 weeks. Double-immunofluorescence staining was then performed to detect BrdU and tyrosine hydroxylase (TH)-positive neurons. The results indicated that the rotation behavior of rats in mesencephalon NSCs+cytokines group was obviously ameliorated, whereas the improvement of rotation in mesencephalon NSCs alone group was less. There was no distinct changing in rotation behavior in cortical NSCs+cytokines group, cortical NSCs alone group and saline control group. The double-immunofluorescence staining results showed that more BrdU and TH double-labeled cells were detected in mesencephalon NSCs+cytokines group and mesencephalon NSCs alone group than those in the other groups. Furthermore, the double-labeled cells in the mesencephalon NSCs+cytokines group was more than that in the mesencephalon NSCs alone group. The present results suggest that grafting mesencephalic NSCs of fetal rats is more effective than grafting cortical NSCs in the treatment of PD model rats. Moreover, these data demonstrate that mesencephalic NSCs can be induced to convert into TH positive neurons by IL-1α, IL-11, LIF and GDNF.更多还原