熟地平颤汤对帕金森病异动症多巴胺D1/D2受体-MAPK/ERK信号转导通路的影响

帕金森病(PD)的主要病理改变是黑质多巴胺(DA)能神经元变性、缺失。左旋多巴(L-Dopa)治疗PD 3-5年后，50%以上的患者会出现运动并发症，其中异动症最为常见，其发作与外源性L-Dopa药物造成对纹状体棘状神经元上DA受体形成异常的波动性刺激，导致受体表达及信号转导通路异常有关。除了经典的多巴胺受体AC/CAMP/PKA通路外，MAPK通路在PD异动症发生机制中同样具有重要的调节作用。本课题在前期工作明确多巴胺D1、D2受体在PD异动症大鼠模型中表达数和活性的改变以及结合滋补肝肾、通络解毒中药治疗后具有肯定疗效的基础上，分别阻断多巴胺D1、D2受体，观察熟地平颤汤对纹状体DA受体后ERK及其上游信号分子Grb2、RAS、Raf、MEK的蛋白基因表达强度以及下游基因IEGs表达量的变化，以期明确中药治疗PD异动症在多巴胺受体MAPK/ERK信号转导通路中的机制。

The major pathology change of Parkinson's disease(PD) is substantia nigra dopamine dopamine and deletion.Above 50% of PD patient well suffer motion complication, especially the evodopa-induced dyskinesias(LID) after 3-5 years levodopa treatment,the reason maybe about striatum acantho- neuron DA acceptor preternatural undulatory stimulus lead to acceptor express and signal transduction access abnormality by levodopa treatment.Besides classical access of DA acceptor AC/CAMP/PKA, MAPK access have the same crucial accommodation in the LIDmechanism.We have found D1、D2 acceptor expression active change in LID Rats and combinated nutritions liver and kidney、dredging collaterals detoxication Chinese medicine would have positive curative effect.In this subject we well discern to block up D1、D2 acceptor,to observe the albumengene expression intensity of ERK and the upper stream signaling molecules Grb2、RAS、Raf、MEK also downstream gene IEGs expression change in striatum DA acceptor after Shu Di Ping Chan Tang treatment.To identify MAPK/ERK signal transduction mechanism of DA acceptor in .LID.