阴虚动风证帕金森病异动症大鼠大麻素CB1受体变化及复方地黄方的干预作用

Effects of compound rehmannia prescription on the cannabinoid receptor 1 in rats with wind syndrome due to deficiency of Yin in levodopa-induced dyskinesia(LID) in Parkinson's disease

目的探讨阴虚动风证帕金森病(PD)异动症(LID)大鼠纹状体内大麻素CB1受体的表达及复方地黄方的干预作用。方法采用6-羟基多巴胺(6-OHDA)偏侧损毁黑质制备帕金森病大鼠模型,进一步腹腔注射左旋多巴+苄丝肼(50 mg/kg左旋多巴和12.5 mg/kg苄丝肼)制备LID大鼠模型,并随机分为LID组、复方地黄方组,另取正常对照组、假手术组大鼠为对照,每组6只。分别在4周、6周进行神经行为学检测后,处死大鼠并取纹状体,应用Western blot法测定各组大鼠纹状体内大麻素CB1受体的表达情况。结果 LID大鼠随造模时间延长,AIM评分呈增加趋势(P<0.05),旋转启动时间呈缩短趋势(P>0.05),旋转持续时间呈增加趋势(P<0.01),剂峰旋转圈数呈减少趋势(P>0.05),复方地黄方可改善上述变化。LID大鼠大麻素CB1受体表达增加,且随造模时间延长呈现减少趋势(P<0.01),而复方地黄方干预后大麻素CB1受体的表达呈现逐渐增加的趋势(P<0.01)。结论LID模型大鼠大麻素CB1受体的含量明显升高,其变化能够较好的反映阴虚动风证的严重程度,复方地黄方干预LID模型大鼠可能是通过激活纹状体内大麻素CB1受体,抑制兴奋性氨基酸(主要是谷氨酸)的释放和诱导细胞发生级联反应来减弱神经元的兴奋性,从而起到减轻L-dopa的兴奋毒性的作用。

Objective To explore the effect of compound rehmannia prescription on cannabinoid receptor 1 in the rats with wind syndrome due to deficiency of Yin in levodopa-induced dyskinesia（ LID） in Parkinson＇s disease. Method A unilateral injection of 6-hydroxydopamine into the substantia nigra was performed to establish a Sprague-Dawley rat model of Parkinson＇s disease. The models were intraperitoneally injected with 50 mg / kg levodopa and 12. 5 mg / kg benserazide for two weeks to prepare LID models with Wind syndrome due to deficiency of Yin. The models were randomly divided into LID group and compound rehmannia prescription groups. Moreover,the normal group and sham-operated group were set up,6 rats in each group. Neurological behavior was tested after treatment for four weeks and six weeks,respectively. Then the rats were sacrificed,the brain was removed immediately and the corpus striatum was dissected out. The expression of cannabinoid receptor 1 was examined by Western blotting. Result With the prolonged time of levodopa treatment,the LID rats with wind syndrome due to deficiency of yin showed an increasing tendency of AIM scores（ P〈0. 05）,shortening of the rotation start time（ P〉0. 05）,a tendency of increased duration of continuous rotation time（ P〈0. 01） and a reducing tendency of peak rotation rate（ P〉0. 05）. Compound rehmannia prescription improved the above mentioned neurological behavior. The expression of cannabinoid receptor 1 showed an increasing tendency in the LID groups compared with that in the normal groups. But with the prolonging time of levodopa treatment,the expression of cannabinoid receptor 1 in the LID groups showed a decreasing tendency（ P〈0. 01）. The expression of cannabinoid receptor 1 had an increasing tendency after the treatment with compound rehmannia prescription（ P〈0. 01）. Conclusions The expression of cannabinoid receptor 1 has an increasing tendency in LID rats with wind syndrome due to deficiency of yin. The changes can well reflect the severity of wind syndrome due to deficiency of yin. We would hypothesize that the treatment with compound rehmannia prescription may activate the cannabinoid receptor 1 in LID rats,inhibiting the release of excitatory amino acids,decreasing the excitability of neurons and inducing cell cascade,and finally reduce the excitatory toxicity of levodopa.