作　　者： ; ; ; ; ; ; ; ;

机构地区： 海南省人民医院

出　　处： 《中山大学学报（医学科学版）》 2009年第5期522-526,共5页

摘　　要： 【目的】探讨Nurr1基因修饰的人脐血间充质干细胞(HUCB-MSC)源性的多巴胺能神经元移植对帕金森病(PD)模型鼠的治疗作用。【方法】SD大鼠PD模型随机分为假手术组(A组)、单纯HUCB-MSC组(B组)、Nurr1基因修饰HUCB-MSC组(C组)。将HUCB-MSC及Nurr1基因修饰后的HUCB-MSC体外分化为多巴胺能神经元,并通过立体定向的手段将其移植入毁损侧纹状体,观察移植前后PD模型大鼠旋转行为的变化和脑内多巴胺(DA)含量的改变,以及纹状体区酪氨酸羟化酶(TH)表达的变化。【结果】B、C两组在移植后第2周、4周和8周时旋转行为及脑内DA含量均较A组有所改善(P<0.05,P<0.01),且B、C组间比较C组改善明显(P<0.05),这种差异以第8周时最为明显。移植后B、C两组TH表达较A组明显增高,并随着时间的增加而逐渐增高,且C组在各时间点上TH表达较B组含量高(P<0.05),并在移植后第8周时最为明显。【结论】Nurr1基因修饰HUCB-MSC来源的多巴胺能神经元移植治疗PD模型鼠,能有效地增加鼠脑内多巴胺含量和纹状体区TH的表达,改善PD模型鼠的症状,为细胞移植治疗PD提供了一种崭新的手段。 【Objective】 To observe the therapeutic effect on rat model of Parkinson＇s disease （PD） by transplantation of dopaminergic neuron derived from human umbilical cord blood mesenchymal stem cells （HUCB-MSC） modified by Nurr1 gene. 【Methods】 Forty-five SD rat model of PD were grouped randomly into sham operation group （group A）, HUCB-MSC transplantation group （group B） and Nurr1 gene modified HUCB-MSC group （group C）. HUCB-MSC and Nurr1gene modified HUCB-MSC were differentiated to dopaminergic neuron and then transplanted into impair striatum of rat PD model. Rotational behavior examination was carried out at different time point after transplantation. Dopamine content and the expression of tyrosine hydroxylase （TH） in rat striatum were detected at the same time point as well. 【Results】 The rat rotational behavior was improved and dopamine content in striatum increased obviously in group B and C as compared with group A at the 2nd, 4th, and 8th week after transplantation （P〈0.05 and P〈0.01, respectively）. These changes were more significant in group C than that in group B at each time point after transplantation （P〈0.05） and the differences reached the most obvious at 8th week after transplantation. Meanwhile, TH expression in rat striatum in group B and C increased with time and was higher than that in group A （P〈0.01）, furthermore, it was higher in group C than that in group B after transplantation （P〈0.05）, and the differences reached most obvious at the 8th week. 【Conclusion】 Transplantation of dopaminergic neurons derived from HUCB-MSC modified with Nurr1 can elevate the DA content, increase the expression of TH in rat brain and improve the symptoms of rat model of PD effectively, which provide a new strategy for cell transplantation therapy for PD.

关 键 词： 基因 人脐带血 间充质干细胞 多巴胺能神经元 帕金森病

领　　域： [生物学]