神经酸对帕金森病模型小鼠运动障碍的缓解作用及机制研究

摘要

目的:研究神经酸对帕金森病(PD)模型小鼠运动障碍的缓解作用及机制.方法:将小鼠随机分为空白对照组(生理盐水)、模型组(生理盐水)、多巴丝肼片组(阳性对照,按左旋多巴计120 mg/kg)和神经酸低、中、高剂量组(20.0、40.0、80.0 mg/kg),每组10只.除空白对照组外,其余各组小鼠均建立PD模型.成模后,每天ig相应药物1次,连续14 d.末次给药后,观察各组小鼠行为学变化,采用高效液相色谱法测定小鼠脑纹状体内多巴胺(DA)及其代谢物二羟苯乙酸(DOPAC)、高香草酸(HVA)的含量.结果:与空白对照组比较,模型组小鼠爬杆时间延长、滚筒时间缩短、自发运动次数减少(P<0.05),脑纹状体内DA、DOPAC、HVA含量均降低(P<0.05).与模型组比较,多巴丝肼片组和神经酸各剂量组小鼠爬杆时间缩短、滚筒时间延长(P<0.05),脑纹状体内DA、DOPAC、HVA含量均升高(P<0.05);多巴丝肼片组和神经酸高剂量组小鼠自发运动次数增加(P<0.05).结论:神经酸可有效改善PD模型小鼠的运动障碍症状,其机制可能与增加脑纹状体内DA含量有关.%OBJECTIVE:To study the alleviation effect of nervonic acid on movement disorder of model mice with Parkinson's disease(PD). METHODS:Mice were randomly divided into blank control group(normal suline),model group(normal saline), Levodopa and benserazide hydrochloride tablet group (positive control,calculated by L-dopamine 120 mg/kg),nervonic acid low-dose,medium-dose,high-dose groups(20.0,40.0,80.0 mg/kg),10 in each group. Except for blank control group,mice in other groups were inducced for PD models. After modeling,mice were intragastrically given relevant medicines,once a day,for 14 d. After the last administration,behavioral changes of mice in each group were observed. HPLC was conducted to detect dopa-mine(DA)and its metabolites dihydroxybenzoic acid(DOPAC),homovanillic acid(HVA)concentrations in the striatum of mice. RESULTS:Compared with blank control group,climbing time was extended in model group,drum time was shortened,spontane-ous movement times was decreased,and DA,DOPAC,HVA contents in the striatum were reduced (P<0.05). Compared with model group,climbing time was shortened in Levodopa and benserazide hydrochlo ride tablet group,nervonic acid dose groups, drum time was extended,and DA,DOPAC,HVA contents in the striatum were increased(P<0.05);and spontaneous movement times was increased in Levodopa and benserazide hydrochloride tablet group,and nervonic acid high-dose group(P<0.05). CON-CLUSIONS:Nervonic acid can effectively improve symptoms of movement dysfunction of model mice with PD. The mechanism may associate with increasing DA content in the striatum.