卞丝肼对6-OHDA损毁大鼠纹状体细胞外多巴胺水平的影响

Effects of benserazide on extracellular dopamine level in striatum of 6-hydroxydopamine-lesioned rats

目的:观察卞丝肼对6-羟多巴胺(6-OHDA)所致帕金森病模型大鼠纹状体细胞外多巴胺(DA)水平的影响。方法:采用6-OHDA建立帕金森病大鼠模型(黑质纹状体去神经支配),用生理盐水制作假损毁大鼠作为对照;而后采用卞丝肼和卞丝肼联合L-多巴胺(L-DOPA)治疗,应用体内微渗析技术分别检测假损毁和6-OHDA损毁大鼠纹状体细胞外DA水平。结果:在假损毁大鼠中,50mg·kg-1卞丝肼可以使细胞外DA水平明显降低(P<0.01)。在6-OHDA损毁大鼠纹状体中,卞丝肼和L-DOPA的共同用药使细胞外DA水平明显升高,但是达到峰值的时间明显延长,并呈现剂量依赖性(P<0.05)。结论:卞丝肼可降低黑质丝状体去神经支配大鼠丝状体氨基酸脱羧酶(AADC)活性,改变外来性L-DOPA的代谢。较高剂量卞丝肼可能会阻止L-DOPA长期治疗所导致的不良反应。

Objective To study the effects of benserazide on extracellular dopamine level in the striatum of 6-hydroxydopamine-lesioned Parkinson＇s disease rat models.Methods The rat models of nigrostriatal denervation of Parkinson＇s disease were set up by using 6-hydroxydopamine（6-OHDA）,and the control rats were treated with isotonic Na chloride.Then the extracellular dopamine（DA）level in the striatum of sham-lesioned rats treated with benserazide alone and in the striatum of 6-OHDA-lesioned rats treated with benserazide in combination with L-DOPA were detected by using in vivo microdialysis technique.Results In sham-lesioned rats,the extracellular DA level was significantly decreased by 50 mg·kg-1benserazide（P〈0.01）.In 6-OHDA-lesioned rats,the extracellular DA level showed a marked increase by the combined use of benserazide and L-DOPA,but the time to reach the peak level was significantly prolonged on a dose-dependent manner（P〈0.05）.Conclusion Benserazide can reduce the central AADC activity in the striatum of rats with nigrostriatal denervation,resulting in changes in metabolism of exogenous L-DOPA.And higher dose of benserazide might be a useful agent to prevent adverse effects of long-term L-DOPA therapy.