颈动脉体球细胞移植治疗帕金森病大鼠的分子机制研究

Study on Molecular Mechanism in Hemiparkinsonian Rat Grafted by Glomus Cells within Carotid Body

目的 :探讨颈动脉体球细胞移植治疗帕金森病 (PD)大鼠的分子机制。方法 :采用 6 羟多巴胺 (6 OH DA)损毁制备偏侧PD大鼠模型 ,于损毁侧立体定向植入自体颈动脉体球细胞块 ,分别对移植后 2和 8周的纹状体组织切片行多巴胺 1受体 (D1R)mRNA(D1)、多巴胺 2受体 (D2 R)mRNA(D2 )、和Nurr相关因子 1(Nurr1)mRNA(Nurr1)的原位杂交分析。结果 :6 OHDA损毁侧纹状体内Nurr1和D1表达显著降低 ,D2 表达增高 ,差异均有显著性 (P <0 .0 1) ;移植后Nurr1仅在移植物内呈高表达 ,而D1表达无明显改变 ,D2 表达则逐渐降低 ,差异有显著性 (P<0 .0 5 )。结论 :移植物内Nurr1表达和D1、D2 表达的变化是颈动脉体球细胞移植治疗的分子调控基础。

Objective: To explore the molecular mechanism in hemiparkinsonian rat grafted by glomus cells within carotid body. Methods: A rat model of hemiparkinsonian was established by microinjection of 6-hydroxydopamine (6-OHDA) solution into right substantia nigra zona compacta. Homo-glomus cells within carotid body were grafted into the right striatum stereotaxically. The grafts differentiated for 2 and 8 weeks respectively and were then subjected to in situ hybridization analysis for the expressions of D 1R mRNA, D 2R mRNA and Nurr1 mRNA. Results:The expression of D 1R mRNA and Nurr1 mRNA in 6-OHDA affected side was significantly decreased. D 2R mRNA was significantly elevated as compared with those in intact side (P<0. 01). After grafting, Nurr1 mRNA was only highly expressed within glomus cells, while no obvious change in D 1R m RNA expression was found and the expression of D 2R mRNA at 2th and 8th week was gradually decreased (P<0. 05). Conclusion: The expression of Nurr1 mRNA within glomus cells and the changes of D 1 RmRNA and D 2RmRNA expression in host striatum were the basis of the molecular modulation in hemiparkinsonian rat grafted by glomus cells within carotid body.