Kim Seung-Nam, Doo Ah-Reum, Park Ji-Yeun, Choo Hyunwoo J, Shim Insop, Park Jongbae J, Chae Younbyoung, Lee Bena, Lee Hyejung, Park Hi-Joon
Acupuncture and Meridian Science Research Centre (AMSRC), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Acupuncture and Meridian Science Research Centre (AMSRC), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Brain Res. 2014 Jan 28;1544:33-44. doi: 10.1016/j.brainres.2013.11.028. Epub 2013 Dec 7.
This study first showed the behavioural benefits of novel combination therapy of L-dopa with acupuncture on Parkinson's disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson's disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining L-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of L-dopa (7.5 mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of L-dopa treatment (15 mg/kg) only, and that (2) the combination treatment (L-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of L-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard L-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of L-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of L-dopa on motor function with reduced dose of L-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia.
本研究首次展示了左旋多巴与针灸联合新疗法对帕金森病的行为益处及其在基底神经节中的潜在机制。先前的研究报道,针灸可能通过增加多巴胺外流和多巴胺周转率来改善帕金森病(PD)小鼠模型的运动功能。因此,我们假设左旋多巴与针灸联合应用对帕金森病患者具有行为益处。我们对C57Bl/6小鼠的纹状体进行单侧注射6-羟基多巴胺以模拟半帕金森病特征。为了测试运动功能和运动障碍异常,我们分别检查了圆筒行为和异常不自主运动(AIM)。我们发现:(1)50%剂量降低的左旋多巴(7.5毫克/千克)与针灸联合应用显示出的运动功能改善与仅给予标准剂量左旋多巴治疗(15毫克/千克)的小鼠相当;(2)当使用等量左旋多巴时,联合治疗(左旋多巴+针灸)在降低AIM评分方面明显更优。与标准左旋多巴治疗相比,联合治疗还显著降低了黑质中GABA含量的异常增加。此外,联合治疗减轻了纹状体中FosB的异常表达,FosB是左旋多巴诱导的运动障碍(LID)的即刻早期基因。所有这些结果表明,针灸通过降低左旋多巴剂量增强了其对运动功能的益处,并通过使基底神经节内的神经化学失衡正常化来减轻LID。