鱼藤酮致鼠黑质脑片多巴胺能神经元损伤的实验研究  

A study of neurotoxicity of rotennone on dopaminergic neurons in the cultured slices of the substantia nigra in rats

作　　者：张麟伟[1] 王涛[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉硕士研究生430022

出　　处：《卒中与神经疾病》2008年第4期209-212,256,共5页Stroke and Nervous Diseases

摘　　要：目的探讨低剂量鱼藤酮对乳鼠中脑黑质脑片多巴胺能神经元的毒性作用及依达拉奉的保护作用。方法取Wistar乳鼠中脑黑质脑片进行培养,酪氨酸羟化酶(TH)免疫组化染色观察多巴胺神经元毁损情况,western-blot测定各组脑片α-突触核蛋白(α-Synuclein)含量,扫描电镜观察脑片超微病理结构变化。结果黑质脑片多巴胺神经元的数目随鱼藤酮浓度及培养时间的增加而明显减少,多巴胺神经元的超微病理显示氧化应激性损害,α-Synuclein的含量随鱼藤酮浓度的增加而升高,依达拉奉+鱼藤酮组较鱼藤酮组能够减少多巴胺能神经元的凋亡并使α-Synuclein的表达量减少。结论成功利用黑质脑片器官型培养体系建立了帕金森病(Pakinson’s disease)模型;低剂量鱼藤酮导致选择性多巴胺神经元的凋亡,并导致α-Synuclein的含量增加,自由基清除剂依达拉奉对此有保护作用。Objective To investigate the early neurotoxicity of rotenone on dopaminergic neurons and explore an ideal tissue model and the protective effect of Edaravone. Methods A long-term midbrain slice cul ture system of Wistar postnatal rats was established according to the interface tissue culture method. After ro tenone was added for some time, its toxic effects on the whole slices and the dopaminergic neurons were identified through immunohistochemistry for tyrosine hydroxylase（TH）, detect the levels of α-Synuclein through western-blot,detect ultrastructure though electron microscope. Results In those cultures exposed to rotenone for more than 20 days, the TH positive neurons in tissue dramatically decreased with the concentrations rising, rotenone also induced α-Synuclein aggregation, edaravone has protective effect on these. Conclusions Longtime stable midbrain slice culture system has been set up successfully. The neurotoxicity of rotenone on the whole slices and dopaminergic neurons shows a close and time dependent manner. Rotenone induces α-Synuclein aggregation and oxidative damage in organotypic midbrain slice cultures , edaravone protects slices from rote none-induced oxidative damage.

关 键 词：鱼藤酮 帕金森病 器官型培养 氧化应激 Α-突触核蛋白 依达拉奉 

分 类 号：R742[医药卫生—神经病学与精神病学]