左旋多巴诱发异动症大鼠脑内多巴胺转运体的放射自显影研究

Imaging Study on the Effects of L-DOPA on Dopamine Transporter in Parkinsonian Rats with ^(131)I-FP-β-CIT

目的研究左旋多巴对帕金森病大鼠脑内多巴胺转运体的影响,探讨左旋多巴诱发异动症的可能机制。方法建立右侧毁损帕金森病大鼠模型,采用左旋多巴(20mg.kg-1.d-1)治疗1个月,停药2d后断头取脑,处死前3h尾静脉注射131I-FP-β-CIT,纹状体部位冠状振动切片,磷屏显影。图像分析系统分析每个切片中左、右纹状体区单位面积的特异性放射性摄取,用比值R左/右来评估多巴胺转运体的数量及功能。结果 (1)假手术组大鼠左右两侧右纹状体区多巴胺转运体对131I-FP-β-CIT特异性放射性摄取差异无统计学意义(左侧为419.407±14.267,右侧为437.604±19.046,P>0.05),R左/右=0.96±0.044;图像清晰,对称分布于基底节纹状体区。(2)帕金森病模型鼠损伤侧(右侧脑)放射性摄取明显减少(右侧284.052±105.84,P<0.01),R左/右值升高(R左/右=1.495±0.25,P<0.01),图像明显稀疏;(3)左旋多巴治疗组部分鼠损伤侧(右侧脑)放射性摄取进一步减少(右侧221.799±75.346,P<0.01),R左/右值较帕金森病模型组进一步升高(R左/右=2.06±0.60,P<0.05);图像中右侧基底节纹状体区更加稀疏,临床观察评分有异动症发生(53%)。结论经左旋多巴治疗后部分帕金森病鼠脑内多巴胺转运体的数目及功能进一步下调,对多巴胺能神经元有毒性作用,易促发异动症。

Objective To investigate the effects of L-DOPA （ L-3,4-dihydroxyphenylalanine） administration on cerebral dopamine transporter（ DAT） in parkinsonian rats and correlate the findings to the pathogenesis of L-DOPA induced dyskinesia （ LID） or abnormal involuntary movements （ AIMs） in parkinsonian rats. Methods Here we examined the number and function of DAT in the basal ganglia of 6-OHDA-lesioned hemi-parkinsonian rats and its regulation by L-DOPA. The rats received L-DOPA （ n = 15, 20 mg·kg-1·d-1,L-DOPA group） or Saline （ n = 4,saline,model group） injection once daily for 1 month,respectively. The behavioral changes were observed and AIMs were evaluated. After 1 month,the treatment was stopped for 2 days,then 0. 2 ml of131 I-FP-β-CIT was injected into the rats through vena caudalis,and images of the rats’DATs were acquired 3 h after injection using the storage phosphor plate. Optical density in the striatum of ratswas measured through image analysis and the ratios （ R） of DAT-specific radioactivity uptake of bilateral striatum （ left/right） were compared. Results In parkinsonian rats 53% of them developed AIM after L-DOPA administration （ LID group） . The DAT-specific radioactivity uptake had no difference between bilateral striatum in the sham-operation rats,the average ratio was 0. 96 （ P 0. 05） . In PD model rats,the DAT-specific radioactivity uptake decreased in the lesioned（ right） side and the ratio was increased （ 1. 495,P 0. 01） . After one month L-DOPA treatment,the average ratio was significantly increased in LID group（ 2. 06,P 0. 01） . Compared with the model group,the differences were significant （ P 0. 05） . Conclusion L-DOPA is toxic to dopaminergic cells and downregulated dopamine binding sites in some parkinsonian rats. That may be involved in the pathogenesis of dyskinesias in PD rats.