早期运动干预对帕金森病模型大鼠黑质多巴胺能神经元电活动的影响

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目的:观察早期运动干预对帕金森病(PD)模型大鼠黑质多巴胺(DA)能神经元自发放电活动的影响,探索运动保护DA能神经元的电生理机制。方法:清洁级SD大鼠40只分为4组:假手术组(Control)和假手术运动组(Control+Ex)各8只、PD组(PD)和PD运动组(PD+Ex)各12只。6-OHDA单侧前脑内侧束注射建立PD模型大鼠,运动组术后24 h开始进行跑台训练,以11 m/min,30 min/day,5day/week训练,共4周。采用玻璃微电极在体细胞外记录法,观察运动对大鼠黑质DA能神经元电活动的影响。结果:PD组大鼠黑质DA能神经元爆发式放电频率和百分比显著高于Control组(P<0.05),放电间隔(ISI)相应缩短(P<0.05);PD+Ex组爆发式放电频率和百分比显著低于PD组(P<0.05),ISI有一定延长(P<0.05)。阿扑吗啡(APO)诱导模型大鼠的旋转行为能力检测发现,4周后PD组大鼠净旋转圈数为261.0±27.1转/30 min,PD+Ex组为230.1±11.4转/30 min,PD+Ex组大鼠异常旋转次数较PD组显著减少(P<0.05)。结论:早期运动干预可部分抑制PD模型大鼠黑质DA能神经元兴奋性,改善PD模型大鼠行为功能。推测早期运动干预引起黑质DA能神经元兴奋性改变的机制可能与运动保护DA能神经元,降低6-OHDA对神经的易损性有关。 OBJECTIVE: To observe the effect of early exercise intervention on the spontaneous electrical activity of dopaminergic neurons in the substantia nigra of Parkinson’s disease (PD) model rats and to explore the electrophysiological mechanism of DA neurons. Methods: Forty clean SD rats were divided into 4 groups: control group, sham operation group (Control + Ex), PD group (PD group) and PD group only. PD model rats were established by injection of 6-OHDA medial forebrain. The exercise group started treadmill training 24 hours after operation and trained at 11 m / min, 30 min / day and 5 days / week for 4 weeks. The effect of exercise on the electrical activity of dopaminergic neurons in substantia nigra of rats was observed by extracellular recording method using glass microelectrode. Results: The frequency and percentage of burst firing of dopaminergic neurons in substantia nigra of PD group were significantly higher than those in Control group (P <0.05) and ISI (P <0.05). The PD + Ex burst frequency And the percentage was significantly lower than that of PD group (P <0.05), ISI was prolonged (P <0.05). In the apomorphine (APO) -induced model rats, the rotational behavior of the rats was detected. After 4 weeks, the net rotation number of rats in PD group was 261.0 ± 27.1rpm / 30min, PD + Ex group was 230.1 ± 11.4rpm / 30min, The number of abnormal rotation in PD + Ex group was significantly lower than that in PD group (P <0.05). Conclusion: Early exercise intervention can partially inhibit the excitability of dopaminergic neurons in the substantia nigra of PD rats and improve the behavioral function of PD rats. It is speculated that the mechanism by which early motor intervention can induce the excitability of DA neurons in substantia nigra may be related to the protection of DA neurons by exercise and the decrease of neuronal vulnerability caused by 6-OHDA.
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