尼古丁对帕金森病大鼠多巴胺能神经元的保护作用  

Protective effects of nicotine on dopaminergic neurons in PD rats

作　　者：张德智[1] 赵青赞[1] 任秀花[1] 张华[1] 周明付[1] 臧卫东[1] 

机构地区：[1]郑州大学基础医学院人体解剖学教研室,郑州450001

出　　处：《郑州大学学报（医学版）》2010年第6期904-907,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金资助项目11700531164

摘　　要：目的:观察尼古丁(NIC)对脂多糖(LPS)诱导的帕金森病大鼠多巴胺能神经元的保护作用。方法:60只大鼠随机分为4组,每组15只。LPS组(L组)、NIC组(N组)和NIC+α7型烟碱乙酰胆碱受体(nAChR-α7)阻断剂α-银环蛇毒素组(α-BTX)(M组)分别腹腔注射PBS、NIC和NIC与α-BTX,连续4周,并于2周末一次性黑质内注射LPS。对照组(C组)均给予PBS。4周末进行阿朴吗啡诱导的旋转试验,并用免疫组化方法观测黑质酪氨酸羟化酶(TH)阳性神经元数量及离子钙结合蛋白1(Iba1)阳性细胞的形态。结果:4组大鼠旋转实验阳性率及30min内旋转圈数差异有统计学意义(χ2=10.179,P=0.006;F=54.681,P<0.001),TH免疫阳性神经元数差异有统计学意义(F=861.541,P<0.001)。与N组相比,L组及M组旋转实验阳性率降低,旋转圈数减少(P<0.05),TH免疫阳性神经元数减少(P<0.05)。N组Iba1阳性细胞多呈静止期的形态;L组与M组细胞形态相似,大多呈活化期的形态。结论:NIC可能通过nAChR-α7抑制小胶质细胞的活化,对LPS诱导的帕金森病大鼠多巴胺能神经元起保护作用。Aim：To observe the protective effects of nicotine（NIC） on dopaminergic neurons of the Parkinson＇s disease（PD） rats induced by lipopolysaccharide（LPS）.Methods：Sixty rats were randomly allocated into four groups.The rats of LPS group （group L）,NIC group （group N） and NIC＋α-bungarotoxin （α-BTX） group （group M） were injected intraperitoneally with corresponding reagents everyday for 4 weeks,and LPS was injected into the substantia nigra（SN） at the end of the 2nd week.Control group （group C） was administered with PBS.Two weeks after LPS injection, rotation test induced by apomorphine was performed,the number of tyrosine hydroxylase（TH） positive neurons was counted, and the morphological changes of ionized calcium-binding protein 1（Iba1） positive cells in the SN were observed by immunohistochemistry.Results：The positive rate of rotation test and the number of rotation circles within 30 minutes among the four groups had significant difference（χ2=10.179,P=0.006;F=54.681,P0.001）,and the number of TH positive neurons had significant difference among the four groups （F=861.541,P0.001）.Compared with group N,the positive rate of rotation test and the number of rotation circles within 30 minutes in group L and group M were significantly reduced（P0.05）,and the amount of TH positive neurons was significantly reduced（P0.05）.Iba1 positive cells were mostly quiescent cells in group N,which were mostly active cells in group L and group M.Conclusion：NIC may inhibit the microglial activation through the nAChR-α7 receptor,thus protect the dopaminergic neurons in the LPS-induced PD rats.

关 键 词：帕金森病 尼古丁 脂多糖 多巴胺能神经元 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]