首乌方对左旋多巴诱发异动症模型大鼠脑内氨基酸类神经递质水平的影响

Effect of shou wu fang on amino acids neurotransmitters in levodopa-induced dyskinesia model rats

目的观察中药首乌方(shou wu fang,SWF)对左旋多巴诱发异动症(levodopa-induced dyskinesias,LID)模型大鼠行为学指标及其脑内氨基酸类神经递质的影响,探讨首乌方干预异动症的作用机制。方法采用6-羟多巴胺(6-hydroxydopamine,6-OHDA)脑内立体定位注射造成偏侧帕金森病(parkinson’s disease,PD)大鼠模型,成模动物灌胃投予左旋多巴(levodopa,L-DOPA)或L-DOPA+不同剂量SWF,分为L-DOPA组、L-DOPA+SWF低剂量组、LID+SWF高剂量组,另设假手术组。所有动物连续给药22 d,给药期间对大鼠进行异常不自主运动(abnormal involuntary movement,AIM)评分。第22天采用微透析技术对清醒大鼠纹状体细胞外液进行取样,并采用高效液相-荧光法检测样本中谷氨酸(glutamate,Glu)、γ-氨基丁酸(GABA)水平动态变化。结果大鼠给服LDOPA后,逐渐出现AIM,至给药结束,与假手术组相比,L-DOPA组AIM评分显著升高(P<0.01);与L-DOPA组相比,L-DOPA+SWF高剂量组AIM评分显著降低(P<0.05)。第22天,与假手术组相比,各给药组大鼠纹状体细胞外液Glu、GABA水平升高,其中L-DOPA组Glu、GABA水平表现出统计学差异(P<0.05);与L-DOPA组相比,L-DOPA+SWF高剂量组Glu水平明显降低(P<0.05)。给药后60 min,L-DOPA+首乌方各剂量组Glu、GABA水平均显著低于L-DOPA组(P<0.05,P<0.01)。结论 SWF能够减轻L-DOPA引起的副反应,改善LID大鼠行为学症状,其作用机制或与其改善LID大鼠脑内异常的氨基酸类神经递质水平有关。

Objective To investigate the effect of SWF on the behaviors and striatal levels of amino acids neurotransmitters of LID model rats,and to explore the effect of SWF on the mechanism of dyskinesias. Methods SD rats were injected with 6-hydroxydopamine（ 6-OHDA） to produce hemi-lateral nitro-striatum lesion. 6-OHDA lesioned rats were daily given L-DOPA,or L-DOPA plus SWF at different doses. Sham group was also established. All rats were treated for 22 days,once per day. During the treatment,abnormal involuntary movements（ AIMs） were evaluated. On 22 nd day,in vivo microdialysis was used to collect striatal extracellular fluid as the rats were in sober and free-moving condition. All dialysates were analyzed by high performance liquid-fluorescence（ HPLC-FLD） detection. Results After treatment of LDOPA,6-OHDA lesioned rats developed AIM. AIM scores of L-DOPA-treated rats were higher than the sham-operated rats（ P 〈0. 01）. L-DOPA plus high dose of SWF-treated rats had lower AIM scores than L-DOPA-treated rats（ P 〈0. 05）. On22 nd day,in L-DOPA-treated rats,striatal levels of glutamate and GABA increased（ P 〈0. 05） than sham group. 60 min after last treatment,levels of glutamate and GABA in L-DOPA-plus SWF-treated rats were significantly lower than the sham-operated and L-DOPA plus SWF-treated rats（ P 〈0. 05,P 〈0. 01）. Conclusions The findings in this study suggested that as SWF was combined,side effects of L-DOPA mitigated as AIMs scale rating were reduced in LID rats.SWF protected 6-OHDA lesioned rats from LID by regulating abnormal striatal concentrations of glutamate and GABA.