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目的探讨丘脑底核(STN)慢性高频电刺激对猴偏侧帕金森病(PD)模型脑内多巴胺(DA)系统的影响。方法采用单侧颈内动脉注入1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)建立猴偏侧PD模型2只,体内植入脑深部电刺激(DBS)系统,行右侧STN慢性高频电刺激。在电刺激前后不同时间点采用微透析技术检测纹状体区细胞外液的多巴胺(DA)及其代谢产物高香草酸(HVA)含量,腰穿取脑脊液标本测量脑脊液中DA、HVA含量,单光子放射计算机断层扫描(SPECT)检测脑内纹状体区巴胺转运体(DAT)及多巴胺D2受体(D2R)的变化。结果猴偏侧PD模型在给予单侧STN慢性高频电刺激后纹状体区DA、HVA明显增高。SPECT显示在有效刺激后纹状体区DAT特异性摄取率增高,D2R特异性摄取率下降。脑脊液中多巴胺及其代谢产物的含量与术前相比无明显差异。结论通过微透析检测提示在给予STN有效慢性高频电刺激后提高了纹状体区DA及其代谢产物的升高,DAT特异性摄取率增高,D2R特异性摄取率下降提示纹状体区的代谢活性有明显升高,这可能是STN-DBS治疗帕金森病的重要机制之一。
Objective To investigate the effect of chronic high frequency electrical stimulation of subthalamic nucleus (STN) on the dopamine (DA) system in the monkey model of hemiparkinsonism (PD). Methods Two hemiparkinsonian PD models were established by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into unilateral internal carotid artery and implanted deep brain stimulation (DBS) System, line right STN chronic high-frequency electrical stimulation. The levels of dopamine (DA) and its metabolite homoelementic acid (HVA) in extracellular fluid of striatum were detected by microdialysis at different time points before and after electrical stimulation. The contents of DA and HVA in cerebrospinal fluid were measured by lumbar puncture in cerebrospinal fluid Changes of dopamine D2 receptor (D2R) and dopamine transporter (DAT) in the striatum of brain were detected by photon emission computed tomography (SPECT). Results The monkey hemiparkinsonism PD model in the unilateral STN chronic high-frequency electrical stimulation striatum DA, HVA was significantly higher. SPECT showed increased DAT-specific uptake in the striatum after effective stimulation, and decreased D2R-specific uptake. Cerebrospinal fluid dopamine and its metabolites content compared with preoperative no significant difference. Conclusions The results of microdialysis suggest that elevated DA and its metabolites in the striatum increase after effective chronic high-frequency electrical stimulation with STN, and the increase of DAT-specific uptake and the decrease of D2R-specific uptake suggest striatal area Metabolic activity was significantly increased, which may be STN-DBS treatment of Parkinson’s disease is one of the important mechanisms.