帕金森病模型大鼠损毁侧纹状体内移植神经干细胞的增殖与分化

Proliferation and differentiation of transplanted neural stem cells in the damaged striatum of Parkinson's disease rats

背景:近年来,细胞移植治疗在帕金森病患者中广为使用,且效果理想。目的:探索帕金森病大鼠移植的神经干细胞的增殖及分化,为帕金森病治疗提供新的理论依据。方法:采用胶原酶消化法体外分离培养大鼠中脑组织中的神经干细胞,诱导第3代神经干细胞。采用6-羟基多巴胺单侧法制作帕金森病大鼠模型,将造模成功大鼠分为模型组和神经干细胞组,各7只。模型组大鼠在损毁侧纹状体内注入4 m L生理盐水,神经干细胞组大鼠在损毁侧纹状体内注射5μL绿色荧光蛋白标记的神经干细胞(1×109 L-1)。结果与结论:神经干细胞组大鼠移植神经干细胞后酪氨酸羟化酶阳性区域面积显著低于模型组,移植神经干细胞后7,14,28 d时Ptx3 m RNA的表达水平显著高于模型组,14,28 d SHH m RNA显著高于模型组,而Nurrl m RNA的表达水平与模型组接近。结果提示神经干细胞移植模型大鼠损毁侧纹状体内可分化为多巴胺能神经元,为治疗帕金森病带来突破性进展。

BACKGROUND： In recent years, cell transplantation therapy is widely used in the treatment of Parkinson＇s disease with satisfactory outcomes. OBJECTIVE： To investigate the proliferation and differentiation of transplanted neural stem cells in Parkinson＇s disease rats, thereby providing a new theoretical basis for the treatment of Parkinson＇s disease. METHODS： Neural stem cells from the brain tissues of rats were isolated and cultured in vitro using collagenase digestion method. Unilateral rat model of Parkinson＇s disease was made by 6-hydroxydopamine method, and the successful rat models were divided into model group and cell transplantation group, with seven rats in each group. The rats in the model group were given 4 mL normal saline at the damaged striatum, and those in the cell transplantation group were injected 5 μL green fluorescent protein-labeled neural stem cells（1×10^9/L） into the damaged striatum. RESULTS AND CONCLUSION： After cell transplantation, the positive area of tyrosine hydroxylase was significantly lower in the cell transplantation group than the model group. Compared with the model group, the expression level of Ptx3 m RNA was significantly higher in the cell transplantation group at 7, 14, 28 days after cell transplantation and the expression of SHH m RNA was significantly higher in the cell transplantation group at 14and 28 days after cell transplantation. However, there was no difference in the expression of Nurrl m RNA between the two groups. These findings indicate that neural stem cells injected into the damaged striatum of rats can differentiate into dopaminergic neurons, which bring a breakthrough in the treatment of Parkinson＇s disease.