卞丝肼对6-OHDA损毁大鼠纹状体AADC活性的影响

Effects of benserazide on AADC activity in the 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芳香L-氨基酸脱羧酶(AADC)活性的影响。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;注射卞丝肼60分钟后,处死大鼠,迅速摘除大脑,并取出纹状体,进行匀浆处理。取匀浆上清液加入到培养基中培养后用高效液相色谱柱(HPLC)进行DA含量测试。结果在假损毁大鼠中,10 mg/kg卞丝肼和50 mg/kg卞丝肼可以使纹状体AADC活性明显降低(P<0.01)。在6-OHDA损毁大鼠纹状体中,10 mg/kg卞丝肼和50 mg/kg卞丝肼明显降低AADC活性,分别为对照物组的25%和12%(P<0.01)。然而,10 mg/kg卞丝肼和50 mg/kg卞丝肼组之间无统计学差异。结论卞丝肼降低6-OHDA损毁大鼠黑质纹状体AADC活性,影响L-DOPA代谢。

Objective To study the effects of benserazide on AADC activity 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.Sixty min after benserazide administration,rats were killed by decapitation and the brains were rapidly removed.The striatum was punched and The tissue was homogenized.Fifty μl of the supernatant was added into An incubation mixture.The amounts of DA formed in the supernatant were determined by HPLC.Results In sham-lesioned rats,the AADC activities was significantly decreased by 10 mg/kg and 50 mg/kg benserazide（P0.01）.In 6-OHDA-lesioned rats,10 mg/kg and 50 mg/kg benserazide significantly decreased AADC activity,which was 25% and 12% of vehicle group（P0.01）.Conclusion These results suggest that benserazide reduces the AADC activity in the striatum of rats with nigrostriatal denervation,resulting in changes in metabolism of exogenous L-DOPA.