大麻素CB1受体在左旋多巴诱导的异动症大鼠基底节的表达研究

Expression pattern of cannabinoid receptor 1 in the basal ganglia of Parkinson disease rat model with levodopainduced dyskinesia

目的观察大麻素CB1受体在长期左旋多巴治疗诱导的异动症(LID)大鼠模型基底节表达的特点,探讨LID与CB1受体表达变化的关系。方法帕金森病(PD)模型大鼠接受左旋多巴腹腔注射21 d,建立LID大鼠模型。采用免疫组化和Western Blot方法检测基底节不同部位CB1受体表达。结果经左旋多巴治疗的PD大鼠出现类似人类LID的行为学表现。免疫组化结果显示LID组纹状体CB1受体损伤侧与未损侧的累积吸光度(IOD)比值下降,而苍白球和黑质网状部该比值升高(均P<0.01);Western blot检测结果与免疫组化显示了相同变化趋势,LID组纹状体CB1受体损伤侧/未损侧条带密度比值降低(P<0.01)。结论长期左旋多巴治疗可引起基底节纹状体CB1受体表达下调,这种改变可能与LID的发生发展有关。

Objective To investigate the expression pattern of cannabinoid receptor 1 （CB1 receptor） in the basal ganglia of Parkinson disease （PD） rat model with levodopa-induced dyskinesia （LID）, and to explore the relationship between LID and the changes of expression pattern of CB1 receptor in the basal ganglia. Methods The PD rats were treated with levodopa to get LID rat models. Immunohistochemistry （IHC） and Western blot were used to observe the changes of CB1 receptor expression in different regions of the basal ganglia of the rat model. Results After the levodopa treatment, PD rat displayed an ethology to resemble the human dyskinesia. The results of IHC demonstrated that the integrated optical density （IOD） ratio of lesioned side over unlesioned side of CB1 receptor in the caudate putamen （CPU） of LID group was obviously decreased, and were increased in the substantia nigra pars reticularis （SNr） and globus pallidous （GP） （both P〈 0.01）. Western blot demonstrated the similar changes in trends as IHC, CB1 receptor＇s expression in the CPU of LID group was significantly decreased by levodopa treatment （P〈0.01）. Conclusions The chronic treatment of levodopa can decrease the expression pattern of CB1 receptors in CPU, which may play an important role in the pathogenesis development of LID.