帕金森病异动症与黑质损伤程度关系的实验研究

The relationship between the dyskinesia in Parkinson disease and the degree of substantia nigra lesion

目的探讨帕金森病(PD)异动症的产生与黑质损伤程度之间的关系。方法通过6-羟基多巴立体定向注射至大鼠前脑内侧束建立PD模型,左旋多巴甲酯腹腔注射治疗(25 mg·kg^(-1)·d^(-1),每天2次)21 d,评估异常不自主运动的情况；然后取中脑,行酪氨酸羟化酶免疫组织化学染色,观察黑质多巴胺能神经元的损伤程度；异常不自主运动积分与黑质损伤程度之间的关系应用Excel软件的S方程分析进行评价。结果25只大鼠经阿朴吗啡诱导后有10只旋转频率＞7次/ min,被认为是成功PD模型；经左旋多巴治疗后,10只PD大鼠中有8只出现了异常不自主运动,包括刻板动作和对侧旋转行为,并且每只大鼠的异常不自主运动均不同；异常不自主运动在黑质酪氨酸羟化酶阳性神经元的损伤达90%以上的PD大鼠中出现；黑质损伤程度和异常不自主运动的发生及程度呈正相关。结论黑质损伤严重程度在PD患者出现异动症中可能起重要作用。

Objective To explore the relationship between the genesis of dyskinesia and the degree of substantia nigra lesion in Parkinson disease（PD）. Methods The hemi-parkinsonian rat model was established by injecting 6-OHDA stereotaxieally to right medial forebrain bundle （MFB）. Then the hemi-parkinsonian rat was injected intraperitoneally with levodopa methylester （25 mg · kg^-1·d^-1 , twice a day） for 21 days, the abnormal involuntary movements were estimated. After being sacrificed, the midbrain was removed, and the injured degree of dopaminergie neurons at substantia nigra was observed by tyrosine hydroxylase immunohistoehemistry staining. The relationship between the abnormal involuntary movement scores and dopaminergie neurons loss at substantia nigra was evaluated by sigmoid equation analysis by using Excel software. Results The apomorphine-indueed rotation rate above 7 r/min was found in 10 of 25 rats, those rats were regarded as successful hemi-parkinsonian model rats. After the treatment with levodopa methylester, 8 of 10 rats displayed abnormal involuntary movements, including stereotype and eontralateral rotation, the types of movements varied. Abnormal involuntary movements were appeared in the rats with dopaminergie neurons loss above 90%. The positive relationship was observed between the degree of lesion in substantia nigra and the severity of abnormal involuntary movements. Conclusions The severe loss of dopaminergie neurons at substantia nigra probably plays a role in the development of levodopa-indueed dyskinesia in patient with Parkinson disease.