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目的观察运动对帕金森病(parkinson’s disease,PD)模型大鼠初级运动皮层(M1)异常β振荡的调节作用,探究运动干预改善PD行为功能的可能原因。方法清洁级SD大鼠18只分为3组,即假手术组(Control,n=5)、PD组(PD,n=6)和PD运动组(PD+Ex,n=7),于内侧前脑束注射6-羟基多巴(6-OHDA)同时于M1区植入多通道电极。大鼠在造模后第1周颈部皮下注射阿朴吗啡(APO)旋转行为实验评价模型成功;PD+Ex组在第1周开始进行跑台训练(11 m/min,30 min/d,5 d/周,4周),各组大鼠在第0/1/2/3/4采用自主错步仪进行行为测试;采用在体多通道电生理技术,观察各组大鼠M1区在第0/1/2/3/4的局部场电位(LFPs),免疫组化技术检测黑质和纹状体内酪氨酸羟化酶(TH)表达。结果 TH免疫组化结果显示,PD+Ex组较PD组无显著性改变(P>0.05);自主错步行为测试结果发现,PD+Ex组的通过时间、前肢错步数和尾部滑落数及潜伏期较PD组均有显著性改善(P<0.01)。电生理学结果显示,PD组较Control组10~30 Hz的β频段异常增高(P<0.01);PD+Ex组在第1周β振荡的PSD较第0周无显著改变(P>0.05),在第2/3/4周(P<0.05)显著降低。结论运动干预调节运动皮层的功能活性,抑制M1区异常β振荡,进而改善其步态及自主活动能力。推测运动降低PD模型大鼠M1区异常β振荡介导了皮层-纹状体Glu能突触可塑性,调控输入至基底神经节的运动编码信息,最终改善大鼠的行为功能。
Objective To observe the effect of exercise on the abnormal β oscillation of primary motor cortex (M1) in Parkinson’s disease (PD) rats and to explore the possible reasons for the effect of exercise intervention on PD behavior. Methods Eighteen SD rats were divided into 3 groups: sham operation group (PD group, n = 5), PD group (n = 6) and PD group The 6-OHDA (6-OHDA) was injected into the forebrain bundle while the multi-channel electrode was implanted in the M1 region. Rats were subcutaneously injected apomorphine (APO) in the first week after modeling to evaluate the rotational behavior of the model. PD + Ex group started treadmill training at the first week (11 m / min, 30 min / d, 5 d / week, 4 weeks). The rats in each group were subjected to behavioral tests on the 0/1/2/3/4 day by using the independent step-by-step instrument. In vivo multi-channel electrophysiological techniques, Local field potentials (LFPs) on 0/1/2/3/4 and tyrosine hydroxylase (TH) expression in substantia nigra and striatum were detected by immunohistochemistry. Results The results of TH immunohistochemistry showed that PD + Ex group had no significant difference compared with PD group (P> 0.05). The results of independent misdiagnosis test showed that passage time, forelimb staggered number, The latency was significantly improved compared with PD group (P <0.01). The electrophysiological results showed that the β-band in PD group was significantly higher than that in Control group at 10-30 Hz (P <0.01), while the PSD of PD + Ex group in the first week did not change significantly (P> 0.05) At 2/3/4 weeks (P <0.05), there was a significant decrease. Conclusion Exercise intervention regulates the functional activity of motor cortex and inhibits the abnormal β oscillation in M1 region, thus improving its gait and autonomic activity. It is hypothesized that exercise induced abnormalβ oscillations in the M1 region of PD rats mediate the synaptic plasticity of Glu in the cortex and striatum and regulate the movement coding information input to the basal ganglia, ultimately improving the behavioral function in rats.