骨髓间充质干细胞、过表达Nurr1蛋白的骨髓间充质干细胞与胎脑细胞移植治疗帕金森病大鼠的比较  

Comparison of transplantation of mesenchymal stem cells and Nurr1-overexpressing mesenchymal stem cells with fetal ventral mesencephalic cells in Parkinson disease rat model

作　　者：徐浩文[1] 孙石磊[1] 

机构地区：[1]郑州大学第一附属医院神经内科,郑州市450052

出　　处：《中华实用诊断与治疗杂志》2011年第10期967-969,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金面上项目资助(30570624)

摘　　要：目的探讨骨髓间充质干细胞(mesenchymal stem cell,MSC)和过表达Nurr1蛋白的MSC移植治疗帕金森病(Parkinson disease,PD)的效果。方法携带Nurr1基因的真核表达质粒pcDNA3.1/Nurr1转染大鼠MSC,构建稳定高表达Nurr1蛋白的MSC克隆(Nurr1-MSC);分别将Nurr1-MSC(Nurr1-MSC组)、MSC(MSC组)、胎鼠中脑腹侧细胞(VMC组)及生理盐水(对照组)植入PD大鼠纹状体,检测移植区Nurr1蛋白表达,观察移植前、后PD大鼠旋转行为变化,评估不同细胞移植治疗PD大鼠效果。结果移植术后8周内,Nurr1-MSC持续高表达Nurr1蛋白,3种移植细胞均明显改善PD大鼠症状(P<0.01),VMC组疗效最佳且持久;Nurr1-MSC组4周内效果优于MSC组(P<0.05),随时间延长其疗效逐渐减弱,至术后8周时与MSC组差异无统计学意义(P>0.05)。结论 MSC及Nurr1-MSC移植PD大鼠纹状体后均可改善PD症状,Nurr1-MSC治疗PD大鼠模型效果短期内优于MSC,长期效果与MSC接近,胎鼠中脑腹侧细胞治疗效果最佳。Objective To explore the effect of mesenchymal stem cell （MSC） and neuro-protection through delivery of Nurr1 by MSC in Parkinson disease rat model. Methods The eukaryotic expression plasmid pcDNA3.1/Nurr1 containing Nurr1 gene was transfected into MSC. The recombinant plasmid was transfected into MSC and constructed cell clone （Nurr1-MSC）. Fetal ventral mesencephalic cell （VMC） and normal saline were used as positive control and negative control respectively. MSC, Nurr1-MSC, VMC and normal saline were injected into the striatum of rats respectively. The expression of Nurr1 and rotational behavior were observed. Results After intrastriatal grafting, Nurr1-MSC stably overexpressed Nurr1 for at least 8 weeks. Nurr1-MSC, MSC and VMC remarkably improved the circling behavior lasting at least 8 weeks in comparison with normal saline（P〈0.01）. The effect of VMC group was the best and most enduring. The therapeutic effect of Nurr1-MSC group was better than that of MSC group in 4 weeks（P〈0.05）, and decreased as the time went on. There was no significant difference in 8 postoperative weeks between Nurr1-MSC group and MSC group（P〈 0.05）. Conclusion Nurr1-MSC, MSC and VMC can improve the symptom of Parkinson disease in rat model. The short-term therapeutic effect of Nurr1-MSC is better than that of MSC. The long-term effects of both cells are similar. The therapeutic effect of VMC is the best.

关 键 词：帕金森病 NURR1基因 骨髓间充质干细胞 胎脑细胞 

分 类 号：R742.5[医药卫生—神经病学与精神病学]