高表达△FosB对帕金森病异动症大鼠纹状体区运动环路的调节作用-神经病学专业论文.docxVIP

华中科技大学硕士学位论文 华 中 科 技 大 学 硕 士 学 位 论 文 PAGE 5 PAGE 5 Regulation role of overexpression of ?FosB to the signal pathways in the striatum of levodopa-induced dyskinesia of hemiparkinsonian rats Abstract Objective To explore the relationship of overexpression of ?FosB in the striatum of hemiparkinsonian rats and levodopa-induced dyskinesia (LID). And to study its regulation to the expression of prodynorphin (PDyn), preproenkephalin (PPE) and glutamic acid decarboxylase 67 (GAD67) in the striatum. Methods Hemiparkinsonian rat models were established by stereotaxical injection of 6-hydroxydopamine (6-OHDA) in the left medial forebrain bundle (MFB). The PD rats injected by recombinant adenoassociated virus vectors with ?FosB and EGFP cDNA (rAAV2-?FosB-EGFP) in the lesioned striatum as the experimental group. The PD rats injected by recombinant adenoassociated virus vectors with EGFP cDNA (rAAV2-EGFP) in the lesioned striatum as the control group.They were divided into 3,6,9,12-week groups at random respectively, the behavior changes and abnormal involuntary movement (AIM) rations to levodopa were observed. Immunohistochemistry staining technique and western blotting were used to detect the quantitive expression of FosB/?FosB in the striatum. Levels of prodynorphin, preproenkephalin and GAD67 mRNA were measured by in situ hybridization histochemistry. Results In rAAV2-?FosB-EGFP groups, the AIM scores increased gradually (P0.01), the expression of FosB/?FosB in the lesioned striatum increased as the weeks continue (P0.01). At the same time, the levels of PDyn, GAD67 mRNA in the lesioned striatum increased gradually (P0.01), but the preproenkephalin mRNA were not changed obviously (P0.05). In rAAV2-EGFP groups, the changes between different-week groups were not obvious compared with the rAAV2-?FosB-EGFP groups. There were significant changes in the lesioned striatum with the intact stiatum in every groups (P0.01). Conclusions Injection of overexpression of ?FosB in