卞丝肼对6-OHDA损毁大鼠纹状体细胞外多巴胺水平的影响

J4 ›› 2010, Vol. 36 ›› Issue (4): 660-663.

卞丝肼对6-OHDA损毁大鼠纹状体细胞外多巴胺水平的影响

沈活¹|王医术²|翟颖仙²|王建伟²

1.延边第二人民医院神经内科|吉林 |延吉 |133001;2.吉林大学基础医学院　病理生物学教育部重点实验室|吉林长春 130021

收稿日期:2009-03-28 出版日期:2010-07-28 发布日期:2010-07-28
通讯作者: 王建伟（Tel：0431-85619481，E-mail：wjw@jlu.edu.cn） E-mail:wjw@jlu.edu.cn
作者简介:沈活（1962-）|男|吉林省延吉市人|副主任医师|医学博士|主要从事神经医学方面研究。
基金资助:
吉林省科技厅杰出青年科学研究计划项目资助课题（20070132）

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

CHEN Huo¹, WANG Yi-Shu², DI Ying-Xian², WANG Jian-Wei²

1.Department of Neurology|Yanbian Second People’s Hospital|Yanbian 133001, China；2.Key Laboratory of Pathobiology, Ministry of Education, School of Basic Medical Sciences,Jilin University, Changchun 130021, China

Received:2009-03-28 Online:2010-07-28 Published:2010-07-28

摘要/Abstract

摘要：

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，50 mg?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。

关键词: 卞丝肼；多巴胺；动物模型；微渗析技术；芳香氨基酸脱羧酶

Abstract:

Abstract: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.

Key words: benserazide, L-DOPA, dopamine, animal model, microdialysis, aromatic L-amino acid decarboxylase

中图分类号:

R971.5

沈活, 王医术, 翟颖仙, 王建伟. 卞丝肼对6-OHDA损毁大鼠纹状体细胞外多巴胺水平的影响[J]. J4, 2010, 36(4): 660-663.

CHEN Huo, WANG Yi-Shu, DI Ying-Xian, WANG Jian-Wei. Effects of benserazide on extracellular dopamine level in |striatum of　6-hydroxydopamine-lesioned rats[J]. J4, 2010, 36(4): 660-663.