【摘要】 目的:观察MPTP对小鼠黑质致密部(SNpc)和腹侧被盖区(VTA)多巴胺(DA)能神经元损伤的差异。方法:按20 mg/kg的剂量每2 h腹腔注射MPTP 0.1 mL,共注射4次制作小鼠急性损伤模型。(1)行为学测试:通过爬杆实验和悬杆实验,分别检测给药后不同时间点小鼠运动迟缓症状和肢体僵硬症状的程度;(2)免疫荧光:检测小鼠SNpc和VTA脑区的DA能神经元标志物酪氨酸羟化酶(TH)。结果:MPTP急性损伤后小鼠出现运动迟缓和肢体僵硬的表现;SNpc脑区的DA能神经元在各时间点均有减少,其中1 d组减少最显著,达69%(P<0.001),其DA能神经元突起亦变短或消失;VTA脑区的DA能神经元在各时间点亦有所减少,只是其幅度(23%)比SNpc脑区小。结论:小鼠急性损伤模型能选择性损伤SNpc和VTA脑区的DA能神经元,损伤快且严重,并在行为学上也有改变,能较好地模拟人类PD的神经病理学改变。更多还原

【Abstract】 Objective: To observe the variability damage of dopaminergic neurons in SNpc and VTA regions of the mouse model induced by MPTP.Methods:(1)Behavioral tests: Using pole test and bar test to observe the degree of bradykinesia and cataleptic symptoms of mice at different time point after administration of MPTP.(2)Immunofluorescence: To detect dopaminergic neurons in SNpc and VTA regions.Results: Compared with saline group,different degree of bradykinesia and cataleptic symptoms of mice were observed and the number of TH positive neurons in SNpc and VTA regions reduced differently after administration of MPTP.On day1,neurons in SNpc were markedly decreased to 31%(69% lost,P<0.001),but in VTA,just 23% lost.We also found the processes were shorter or disappeared.Conclusion: MPTP(20 mg/kg i.p,four times at 2 h intervals within a day) can selectively injury the dopaminergic neurons in SNpc and VTA regions.The injury was acute and severe.The behavior of the mouse was also detectable.The changes of neuropathology were similar to those in human Parkinson’s disease.更多还原