血清miRNA-181a在帕金森病中神经保护作用及机制分析  

A study of neuroprotective mechanism of serum miRNA-181a in Parkinson's disease

作　　者：孔程程 杨文平 华建 刘妍 丁海霞 

机构地区：[1]南京医科大学第一附属医院老年神经科,江苏南京210029 [2]无锡锡山人民医院神经内科,江苏无锡214011 [3]南京医科大学药学院干细胞与神经再生研究所,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2017年第9期1081-1085,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81100835)

摘　　要：目的:探讨miRNA-181a对l-甲基-4-苯基吡啶离子(1-methyl-4-phenyl-pyridinium,MPP+)诱导的帕金森病(Parkinson’s disease,PD)多巴胺能神经元损伤的影响及其相关机制。方法 :采用胎龄12.5 d的C57BL/6小鼠胚胎中脑进行多巴胺能神经元原代培养,依据不同处理方法分为4组:(1)空白对照(Control)组;(2)PD模型(MPP+)组;(3)阴性对照(miRNA-NC+MPP+)组;(4)miRNA-181a+MPP+组。酪氨酸羟化酶(tyrosine hydroxlase,TH)可以选择性标记多巴胺能神经元,因此采用荧光显微镜对各组TH染色阳性神经元数目、初级突触分枝及最长突触长度进行观察,分析各组之间的差异。结果:Control组多巴胺能神经元细胞体积较大,呈圆形或三角形,胞体发出1个、2个或多个长的分枝以及轴突发出的次级突起,胞体和轴突表面光滑,形态完整,神经元分枝之间相互交织呈网络,联系密切。miRNA-NC+MPP+组经MPP+作用后多巴胺能神经元的数量减少,绝大多数表现为胞体存在,分枝数目及最长突触长度明显减少,网状交织稀少,表面不光滑,有的呈串珠样肿胀或轴突中断、丢失,仅存胞体,少数也表现为胞体空虚、丢失,仅存突起。miRNA-181a+MPP+组较miRNA-NC+MPP+组多巴胺能神经元数目有所增加,胞体形态较好,分枝数目与最长突触长度较miRNA-NC+MPP+组有所改善,且表面较光滑,神经元死亡程度较低。结论:miRNA-181a对MPP+所致多巴胺能神经元损伤起到神经保护作用。Objective：To investigate the neuroprotective mechanism of serum miRNA-181 a on dopaminergic neurons in primary cell model of Parkinson＇s disease induced by 1-methyl-4-phenyl-pyridinium （MPP＋）.Methods：Embryonic mouse mesencephalic primary neurons were cultured in vitro and divided into four groups：a blank control group,a MPP＋group,a miRNA-NC＋MPP＋ group,a miRNA-181a＋MPP＋group.Dopaminergic neurons dendrites and axons were identified and counted by using tyrosine hydroxlase （TH） immunostaining under microscope in each group.Results：The dopamin （DA） neurons exhibited intact circular or triangular bodies and a variety of dendrites and axons derived from bodies,and had intact morphous and interweaved closely in the control group.The group treated by MPP＋were specifically found that the number of dopaminergic neurons decreased strikingly,axons and dendrites disappeared completely,and bodies remained.The axons appeared abnormal varicosities,apparent string-of-beads change.The axons and dendrites almost fragmented,only few cell bodies disappeared and exhibited axonal root.In the MPP＋group,the number of dopaminergic neurons increased,and cell bodies,axons,dendrites and the death of the dopaminergic neurons became improvement.Conclusion：The results suggested that miRNA-181 a may play an important role in protecting dopaminergic neurons in MPP＋ induced Parkinson＇s disease.

关 键 词：miRNA-181a 帕金森病 原代培养 多巴胺能神经元 神经保护 

分 类 号：R742.5[医药卫生—神经病学与精神病学]