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目的研究左旋多巴对黑质细胞的神经毒性作用,探讨左旋多巴治疗帕金森病(PD)的最佳方案。方法选用Wistar大鼠,采用改良的Thomas方法,用6-OHDA行脑立体定向注射术制作大鼠帕金森病(PD)模型100只,随机分为两大组:PD模型组(n=25)、L-dopa治疗组(n=75),采用TUNEL方法观察左旋多巴小、中、大3种不同剂量犤10,50,100mg/(kg·d)犦、不同的作用时间(1,3,5,7d)对帕金森病大鼠黑质细胞的毒性作用,并观察治疗后7d各项指标的变化。结果同一时点PD大鼠黑质细胞凋亡数随着左旋多巴治疗的时间、剂量增加而增加;1～7d小剂量组:从(412±35)个/mm2减少到(403±22)个/mm2,中剂量组从(468±33)个/mm2增加到(605±37)个/mm2,大剂量组从(759±61)个/mm2减少到(486±37)个/mm2;7～14d各时点减少。结论左旋多巴能加速PD大鼠黑质细胞凋亡,小剂量、间隔使用左旋多巴能有效减少其神经毒性作用。
Objective To study the neurotoxic effect of levodopa on the substantia nigra cells and to explore the optimal solution of levodopa in the treatment of Parkinson’s disease (PD). Methods 100 Wistar rats were randomly divided into two groups: PD model group (n = 25), PD model group (n = 25) , L-dopa treatment group (n = 75). TUNEL method was used to observe the effects of levodopa on small, medium and large doses of 10, 50 and 100 mg / (kg · d) 5,7d) on the toxicity of Parkinson’s disease in rat substantia nigra and observe the change of each index 7d after treatment. Results Compared with levodopa treatment, the number of apoptotic normocytes in PD rats increased at the same time point. The numbers of apoptotic normocytes in PD rats increased from (412 ± 35) / mm2 to (403 ± 22) Mm2 in the middle-dose group and increased from (468 ± 33) / mm2 to (605 ± 37) / mm2 in the middle dose group and from (759 ± 61) / mm2 to (486 ± 37) 7 ~ 14d decreased at all times. Conclusion Levodopa can accelerate the apoptosis of substantia nigra in PD rats. Low dose and interval levodopa can effectively reduce the neurotoxic effect.