转录因子EN1在帕金森病模型小鼠中脑表达中的变化  

Expression changes of transcription factor EN1 in the midbrain of mice model of Parkinson's disease

作　　者：谢晓明[1] 刘宏亮[1] 高宇[1] 姚忠祥[2] 詹晓黎[2] 吴永涛[1] 

机构地区：[1]第三军医大学西南医院康复医学科,重庆400038 [2]第三军医大学基础部组织学与胚胎学教研室

出　　处：《中国康复医学杂志》2012年第3期197-200,共4页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金(30672732)项目;第三军医大学青年创新人才基金项目(2009XQN26)

摘　　要：目的:研究小鼠帕金森病(PD)模型急性期中脑转录因子EN1表达变化的特点及小鼠的自发性活动改变。方法:应用6-羟多巴胺(6-OHDA)纹状体注射制备小鼠PD模型;旷场试验观察其行为学变化;免疫组织化学/荧光染色检测注药后24h内中脑EN1、酪氨酸羟化酶(TH)的表达变化。结果:与对照组相比,模型组运动方式明显异常,7d内基本恢复正常;运动总量随注药后时间延长呈恢复趋势,但与对照组对比无显著差异;中央区域活动时间逐渐减少,反映了焦虑指数增高。与对照侧相比,实验侧中脑EN1免疫阳性细胞数在3—9h时已出现减少,12—18h时已较显著,18h为65.2±22.3%(P<0.05),21h时减少非常显著。TH阳性的多巴胺能(DA)神经元数目也随时间逐渐减少,但时间上略晚于EN1,15h才可见减少,18h时减少明显,为68.3±1.2%(P<0.05)。EN1在中脑主要定位于细胞核,但也可见于细胞浆。结论:注射6-OHDA后,小鼠出现行为学改变,焦虑指数增高;实验侧中脑EN1和TH阳性细胞数均随时间逐渐减少且EN1变化早于TH,提示转录因子EN1的减少可能是诱导DA神经元凋亡及PD部分症状出现的重要原因。Objective：To characterize the changes of expression of transcription factor Engraileel 1（EN1） in midbrain and locomotor activity in Parkinson＇s disease（PD） mice model in acute stage after 6-hydroxydopamine（6-OHDA） injection.Method：PD mice models were induced by intra-striatal 6-hydroxydoparnine（6-OHDA） injections.The open-field test was used to assess their behavior.The expressions of EN1 and tyrosine hydroxylase（TH） in midbrain were examined by immunohistochemistry and immunofluorescence in 24h after operations.Result：Compared to control mice,the behaviors of model mice were noticeably affected,which recovered in 7d after injection;their total travel distance recovered after injection as time went over,but didn＇t contrast sharply with control group;the time spent in the centre-area exhibited a gradual diminution which indicated an increased anxious state.Compared with control sides,the expressions of EN1 in experimental sides decreased 3—9h after injection and became apparent after 12—18h with 65.2±22.3%（P0.05） at 18h and significant after 21h.Similar to EN1,the TH-positive dopaminergic neurons reduced over time.But its reductions were later than EN1,with apparent and noticeable changes 15h or 18h after injection,68.3±1.2%（P0.05） at 18h.In the midbrain,EN1 was located mainly in the nucleus and less in cytoplasm.Conclusion：Activities of model group altered and their anxiety index rised after 6-OHDA injection.The EN1 or TH positive neurons both decreased as time went by,with the alterations of EN1 earlier than TH,which might suggest that the apoptosis of dopaminergic neurons and clinical symptoms of PD were related to the reductions of EN1 protein to some extent.

关 键 词：帕金森病 转录因子EN1 酪氨酸羟化酶 多巴胺能神经元 旷场试验 

分 类 号：R742.5[医药卫生—神经病学与精神病学]