帕金森病大鼠黑质细胞凋亡与左旋多巴剂量的关系

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。

Relationship between apoptosis in substantia nigra and dosages of levodopa in rat model of Parkinson's disease

AIM:To evaluate the neurotoxicity of levodopa on substantia nigra and explore the best therapeutic method for Parkinson's disease(PD) by levodopa. METHODS:The rat models of Parkinson disease(PD) were established by injecting stereotaxically 6- OHDA by modified Thomas method.One hundred rat models were randomly divided into two groups:PD model group(n=25) and L dopa treatment group(n=75).TUNEL method was used to observe the neurotoxicity of L dopa on substantia of rats with PD in different dosages10, 50, 100 mg/(kg@ d) ] and at different time(1, 3, 5, 7 day) and changes of 7 items after treatment were observed. RESULTS:Number of apoptic cells in substantia nigra increased with prolonging of treatment duration and increasing of dosage at the same time point;1- 7 day small dosage group:from( 412± 35) /mm2 to ( 403± 22) /mm2;middle dosage group:from( 468± 33) /mm2 to( 605± 37) /mm2;large dosage group:from ( 759± 61) /mm2 to( 486± 37) /mm2; The number decreased at 7- 14 day. CONCLUSION:Levodopa can accelerate apoptosis in substantia nigra and administration of levodopa in a small dosage and intermittently can effectively reduce its neurotoxicity.