【作者】 蒋欣；

【导师】 曹学兵；

【作者基本信息】 华中科技大学 ， 神经病学， 2011， 硕士

【摘要】 目的:研究纹状体区高表达ΔFosB在左旋多巴诱发异动症(LID)中的作用及对皮质纹状体谷氨酸通路的影响。方法:6-羟基多巴立体定向注射建立帕金森病(PD)动物模型,将模型分为两组,纹状体区注射表达ΔFosB的腺相关病毒载体(rAAV2-ΔFosB-EGFP)作为实验组,注射表达EGFP的腺相关病毒载体(rAAV2-EGFP)作为对照组,两组PD大鼠再分为四个亚组分别于注射病毒载体3w、6w、9w、12w后给予一次左旋多巴治疗并进行异常不自主运动(AIM)评分,而后用免疫组化技术检测纹状体FosB/ΔFosB蛋白水平的变化,免疫印记技术检测纹状体区ΔFosB、NMDAR1总蛋白及Ser896位点磷酸化水平的变化。结果: 3w、6w、9w、12w对照组均未出现明显异动症表现,而3w、6w、9w、12w实验组大鼠均出现了典型的异动症,其AIM平均评分分别为22.89±2.53;37.38±4.96;47.38±4.14;50.25±5.23,随时间的延长呈逐渐增高趋势,而各周次对照组均未出现明显的异动症。各周次实验组大鼠损毁侧纹状体区ΔFosB表达量较同周次对照组明显增高,差异有统计学意义;NMDAR1总蛋白及其Ser896位点磷酸化水平较对照组有所增高,差异有统计学意义。结论:大鼠纹状体区ΔFosB的高表达与异动症的发生密切相关,ΔFosB的水平与AIM评分呈正相关,我们可以通过纹状体区注射表达ΔFosB病毒载体复制帕金森病大鼠异动症模型,ΔFosB调节NMDAR1表达及其磷酸化水平可能参与了异动症的发生机制。更多还原

【Abstract】 objective To study the role ofΔFosB high expression in striatum in the development of levodopa-induced-dyskinesia(LID) and the influence on the pathway of glutamate receptors.Methods The hemiparkinsonian rat model was established by 6-hydroxydopamine (6-OHDA) injection stereotaxically.Then the models were divided into two groups: experimental group and control group.The rats in experimental group were used to inject rAAV2-ΔFosB-EGFP stereotaxically, and the rAAV-EGFP was injected into the rats in control group instead.Both of the groups were also divided into four subgroups,the rats in subgroups were kept seperately for 3 weeks,6 weeks,9 weeks and 12 weeks.Then all the rats accept single injection of levodopa, and the AIM scores were evaluated. The expression of FosB/ΔFosB in the striatum was detected by inmunohistochemistry, the changes ofΔFosB, NMDAR1 total protein and NMDAR1 ser896 phosphorylated protein were checked by western blot.Results dyskinesia can not be seen obviously in the rats in control subgroups , All the rats in experimental subgroups showed typical dyskinesia,the AIM scores of 3w,6w,9w and 12w experimental subgroups are separately 22.89±2.53;37.38±4.96;47.38±4.14;50.25±5.23, and as time increased,the AIM scores were increased gradually. The level ofΔFosB in the rats in experimental group were much higher than that in control group. The levels of NMDAR1 protein and NMDAR1 ser896 phosphorylated protein in experimental group were aslo higher than that in control group.Conclusion The striatal high expression ofΔFosB in PD rats were related closely to the development of dyskinesia. The level ofΔFosB was positively correlated to the AIM scores.We can established parkinsonian rat model by injecting rAAV-ΔFosB into the striatum of rats andΔFosB may involve the development of dyskinesia by mediating the expression of NMDAR1 and phosphorylated protein.更多还原