诺米芬新对甲基苯丙胺依赖大鼠多巴胺能神经元毒性的保护作用  

The neuroprotective effects of Nomifensine on dopaminergic neurotoxicity in MA depending rat

作　　者：张岩[1] 杨宇[2] 曾晓锋[1] 赵永和[1] 王尚文[1] 李桢[1] 

机构地区：[1]昆明医学院法医学院,云南昆明650500 [2]重庆市公安局,重庆400000

出　　处：《现代生物医学进展》2010年第22期4209-4213,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(NO30660202);教育部春晖项目(NOZ2006-1-65003);云南省科技厅项目(NO2006GH22)

摘　　要：目的:探索诺米芬辛(Nomifensine)对甲基苯丙胺依赖大鼠多巴胺能神经元毒性的保护作用并探讨其作用机制。方法:Wistar雄性大鼠30只,随机分为生理盐水组、甲基苯丙胺组(MA组)和甲基苯丙胺加诺米芬辛组三组。每晚8时分别腹腔注射Nacl10mg/kg、MA 10mg/kg和MA 10mg/kg+Nomifensine 2mg/kg,连续四天。通过观察动物的刻板行为和条件位置偏爱实验(CPP实验),建立甲基苯丙胺依赖大鼠模型。最后一次给药后的24小时处死各组实验动物,用免疫组织化学染色法(S-P法)和荧光分光光度计法检测大鼠脑内黑质、纹状体内多巴胺神经元细胞的形态和数量的变化,对神经纤维进行灰度值分析。结果:1.生理盐水组分别与甲基苯丙胺组、甲基苯丙胺加诺米芬辛组在刻板行为评分和持续时间上比较呈显著性差异;甲基苯丙胺加诺米芬辛组和甲基苯丙胺组在刻板行为评分和持续时间上比较呈显著性差异;甲基苯丙胺加诺米芬辛组和甲基苯丙胺组在CPP实验结果上比较呈显著性差异。2.通过脑内黑质、纹状体内多巴胺神经元细胞计数、神经纤维灰度值和TH含量荧光分光光度计测量,结果显示甲基苯丙胺加诺米芬辛组神经系统损伤轻于阳性对照组。结论:诺米芬辛对甲基苯丙胺中毒大鼠多巴胺能神经元有保护作用。Objective： To investigate the neuroprotective effects and mechanism of Nomifensine on dopaminergic neurons in MA depending rat. Methods： 30 Wistar male rats were randomly divided into saline group, MA group and MA＋Nomifensine group（protective drug group ）.The rats of saline group were treated by saline 10mg/kg intraperitoneal injection at 8：00 pm each day. The rats of MA group were treated by MA 10mg/kg intraperitoneal injection at 8：00 pm each day. The rats of MA＋Nomifensine group were treated by both MA 10mg/kg and Nomifensine 2mg/kg intraperitoneal injection at 8：00pro each day. Administration time was 8：00pm everyday. Four days after the building of the MA poisoning model, stereotyped behavior and Conditioned Place Preference （CPP） were used to evaluate whether the model was successful. The successfully builded model rats were killed 24h after the last administration. Immunohistochemical method and fluorescence spectrophotometer were used to detect the dopaminergic neurons＇ form and quantity of substantia nigra, midbrain ventral tegmental area on semiquantitative and quantitative aspects. The image analysis system was used to calculate masculine cells. Results： 1. There was obvious statistical significance for stereotyped behavior scores and duration between negative control group and MA＋ Nomifensine group, MA group. There was obvious statistical significance for stereotyped behavior scores and duration between MA＋ Nomifensine group and MA group. There was obvious statistical significance for CPP between MA＋ Nomifensine group and MA group. 2. The effect of protecting the nervous system damage of the drug group was lighter than that ofpositive control group. Conclusion： Nomifensine had neuroprotective effect on MA poisoning rat.

关 键 词：诺米芬辛 甲基苯丙胺 多巴胺能神经元 神经毒性 

分 类 号：Q95-3[生物学—动物学] R421[医药卫生—临床医学]