高频电刺激丘脑底核治疗早期帕金森病大鼠模型的实验研究

High frequency stimulation of subthalamic nucleus (HFS-STN) can increase the striatum dopamine (DA) and its metabolites content to ease the symptoms of advanced Parkinson's disease (PD) movement disorders and thus play an important role in the treatment of PD. HFS-STN has been recognized as an effective method of treatment of advanced PD, however, whether HFS-STN can be used in the treatment of early PD is still unknown, and whether HFS-STN has a protective effect to dopaminergic neurons (DAN) is still controversial. Our study is intended to establish early and advanced PD animal models by 6-OHDA lesioned striatum rats. Then stereotactic surgery buried STN stimulation electrode and high-frequency stimulation of the STN. In order to assess the differences of the early and late applications HFS-STN on PD treatment effect and whether it has a protective effect on the DAN, we apply high performance liquid chromatography method (HPLC), fast cyclic voltammetry (FCV), tyrosine hydroxylase (TH) Western blot, TH immune histochemical method. At the same time monitor the PD rat behavioral changes before and after stimulation, and compare differences in efficacy with optimal medical therapy to provide experimental and theoretical basis for the clinical application of HFS-STN treatment in early PD.

高频电刺激（HFS）丘脑底核（STN）可以增加纹状体内多巴胺（DA）及其代谢产物含量，缓解晚期帕金森病（PD）的运动障碍等症状，从而起到治疗PD的作用。HFS-STN已被公认为晚期PD治疗的有效方法，然而对于HFS-STN能否应用于早期PD的治疗目前尚在研究中，同时对于HFS-STN是否对多巴胺能神经元（DAN）具有保护作用尚有争议。本项目拟以6-OHDA损毁大鼠纹状体，制备早期及晚期PD动物模型，实施立体定向手术埋置STN刺激电极，对STN进行高频电刺激，运用高效液相色谱法（HPLC）、快速周期伏安法（FCV）、酪氨酸羟化酶（TH）Western blot及TH免疫组织化学法，同时监测刺激前后PD大鼠行为学改变，评估早期及晚期应用HFS-STN对PD治疗效果的差异及是否对DAN具有保护作用,并比较与最佳药物治疗方案的疗效差异，为临床应用HFS-STN治疗早期PD提供实验理论依据。

高频电刺激（HFS）丘脑底核（STN）可以增加纹状体内多巴胺（DA）及其代谢产物含量，缓解晚期帕金森病（PD）的运动障碍等症状，从而起到治疗PD的作用。HFS-STN已被公认为晚期PD治疗的有效方法，然而对于HFS-STN能否应用于早期PD的治疗目前尚在研究中，同时对于HFS-STN是否对多巴胺能神经元（DAN）具有保护作用尚有争议。本项目拟以6-OHDA损毁大鼠纹状体，制备早期及晚期PD动物模型，实施立体定向手术埋置STN刺激电极，对STN进行高频电刺激，运用高效液相色谱法（HPLC）、快速周期伏安法（FCV）、酪氨酸羟化酶（TH）Western blot及TH免疫组织化学法，同时监测刺激前后PD大鼠行为学改变，评估早期及晚期应用HFS-STN对PD治疗效果的差异及是否对DAN具有保护作用,并比较与最佳药物治疗方案的疗效差异，为临床应用HFS-STN治疗早期PD提供实验理论依据。本研究发现HFS-STN后SN内TH阳性细胞元数目没有明显增加，但其可以使SN内TH表达增强。本研究证实HFS-STN可以激活黑质纹状体内DAN，调控TH基因表达，增强残存DAN合成DA能力，促进纹状体内DA释放，从而缓解PD症状，这一过程可能并不是通过HFS-STN对DAN的神经保护作用实现的。