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摘要
BACKGROUND: Deep-brain stimulation has proven to be beneficial in the treatment of Parkinson's disease (PD) patients.
OBJECTIVE: To investigate the effects of high-frequency stimulation (HFS) to the subthalamic nucleus (STN) on neuronal apoptosis and apoptosis-related gene expression in the substantia nigra pars compacta. and to analyze the neuroprotective effect of HFS-STN.
DESIGN, TIME AND SETTING: Neuronal morphology experiments were performed in the Beijing Neurosurgical Institute from May to December in 2005.
MATERIALS: Forty healthy, adult, Sprague Dawley rats were used to establish a PD model with a unilateral microinjection of 6-hydroxydopamine into two target areas of the right medial forebrain bundle. 6-hydroxydopamine was purchased from Sigma (USA) high-frequency electrical stimulator was produced by World Precision Instruments (USA); Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) kit was a product of Nanjing Jiancheng, Technology Co., Ltd. (China); and Bcl-2 and Bax protein assay kit were Purchased from Wuhan Boster Bioengineering Co., Ltd. (China).
METHODS: Forty rats were randomly divided into three groups. The stimulation group (n = 15) received HFS-STN on the day of PD modeling. The PD model group (n = 15) was used to establish the PD model. The control group (n = 10) was injected with normal saline containing 0.2 g/L ascorbic acid into two areas of the right medial forebrain bundle.
MAIN OUTCOME MEASURES: Survival of dopaminergic neurons in the substantia nigra pars compacta was determined using Nissl staining. Apoptosis of dopaminergic neurons was detected using TUNEL techniques. Expression of anti-apoptotic protein. Bcl-2, and pro-apoptotic protein, Bax. were assayed by immunohistochemistry.
RESULTS: Following 6-hydroxydopamine injection, the number of substantia nigra pars compacta neurons was reduced in the stimulation and PD model groups, compared to the control group. At 2 and 4 weeks post-surgery, the grey value of Nissl stained images was significantly less in the PD model and stimulation groups (P < 0.05), and the stimulation group exhibited greater grey values compared to the model group (P < 0.05). At 2 and 4 weeks post-surgery, the number of apoptotic neurons was significantly less in the stimulation group compared to the model group (P < 0.05). In addition. Bcl-2 and Bax expression, as well as the Bcl-2/Bax ratio, was much higher in the stimulation group compared to the model group (P < 0.05).
CONCLUSION: HFS-STN has a neuroprotective effect on dopaminergic neurons in the substantia nigra pars compacta of PD rats by promoting Bcl-2 expression, inhibiting Bax expression, and reducing the number of apoptotic dopaminergic neurons.
- 出版日期2008-9
- 单位北京市神经外科研究所; 首都医科大学
