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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 investigate the effect of mesenchymal stem cells (MSCs) and Nurr1 overexpressing MSC transplantation on Parkinson disease (PD). Methods Nurr1-MSC (Nurr1-MSC) was constructed by transfecting rat MSC with Nurr1 eukaryotic expression plasmid pcDNA3.1 / Nurr1. Nurr1-MSC group, MSC (VMC group) and normal saline (control group) were implanted into the striatum of PD rats to detect the expression of Nurr1 protein in the graft area. The changes of the rotational behavior of PD rats before and after transplantation were observed and evaluated Effects of different cell transplantation on PD rats. Results Nurr1-MSC sustained high expression of Nurr1 protein within 8 weeks after transplantation. All the three kinds of transplanted cells significantly improved the symptoms of PD rats (P <0.01) Compared with MSC group (P <0.05), the curative effect gradually weakened with time, and there was no significant difference between MSC group and MSC group after 8 weeks (P> 0.05). Conclusion MSC and Nurr1-MSC transplantation can improve PD in PD rats. The effect of Nurr1-MSC in PD rat model is better than that in MSC in short term, and the long-term effect is close to MSC. optimal.