应用脑微透析技术建立L-DOPA引起的PD大鼠脑氧化损伤的模型  

Establishment of the oxidative damage model in brain of PD rats induced by L-DOPA with microdialysis technique

作　　者：王丹巧[1] 王巍[1] 景富春[2] 赵晋宁[1] 

机构地区：[1]中国中医科学院医学实验中心,北京100700 [2]石河子大学药学院,新疆石河子832002

出　　处：《中国药理学通报》2007年第11期1527-1530,共4页Chinese Pharmacological Bulletin

基　　金：国家中医药管理局资助项目(No04-05ZP65)

摘　　要：目的应用脑微透析技术建立左旋多巴(L-DOPA)引起的PD大鼠脑氧化损伤的模型。方法6-羟基多巴胺(6-OHDA)脑内注射造成PD大鼠模型,采用微透析技术,脑内灌流L-DOPA、水杨酸捕获羟自由基和高效液相-电化学检测,动态观察L-DOPA处理前后大鼠纹状体细胞外液多巴胺(DA)及其代谢产物,羟自由基被捕获所形成的2,3-二羟基苯甲酸(2,3-DHBA)、2,5-二羟基苯甲酸(2,5-DHBA)浓度的变化。结果L-DOPA处理后,模型组大鼠2,3-DHBA和2,5-DHBA浓度分别有6个和7个时间点较对照组明显升高(P<0.05,P<0.01);还原型谷胱甘肽在多个时间点抑制了这种升高(P<0.05,P<0.01)。结论应用脑微透析技术建立L-DOPA引起的PD大鼠脑氧化应激损伤的急性模型,可以进行在体的和动态的监测,为筛选协同L-DOPA治疗PD的抗氧化损伤药物提供有用的方法。Aim To establish the model of oxidative damage in brain of Parkinsons disease（PD）rats induced by levodopa（L-DOPA）with microdialysis technique.Methods PD model rats were induced by intracerebral injection of 6-hydroxyl dopamine（6-OHDA）and were perfused in brain with L-DOPA by using microdialysis technique.Salicylic acid can capture hydroxyl radicals in brain,then yield 2,3-dihydroxy benzyl acid（2,3-DHBA）and 2,5-dihydroxy benzyl acid（2,5-DHBA）.Extracelluler dopamine（DA）and its metabolites,2,3-DHBA and 2,5-DHBA in striatum of rats were measured by HPLC-ED before and after L-DOPA treatment.Results Both 2,3-DHBA and 2,5-DHBA in model group were significantly higher than those in control group at 6 and 7 time points respectively（P〈0.05 or P〈0.01）after treatment with L-DOPA,GSH inhibited these elevations at many time points（P〈0.05 or P〈0.01）.Conclusions Using microdialysis technique and intracerebral perfusion of L-DOPA in PD rats could establish a model of brain oxidative damage with continuous measuring in vivo and provide an available method for treating PD drug screening in cooperation with L-DOPA.

关 键 词：左旋多巴 脑内微透析 羟自由基 6-羟基多巴胺 氧化应激损伤 

分 类 号：R-332[医药卫生] R322.81