PDTC对MPTP帕金森病鼠黑质NF-κB表达的影响

The Effects of PDTC on the Expression of NF-κB in the Substantia Nigra of Parkinson Disease Mouse Model Induced by MPTP

目的研究二硫代氨基甲酸吡咯烷(PDTC)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病(PD)鼠黑质核因子-κB(NF-κB)表达的影响。方法实验组C57/BL小鼠按体重30 mg/(kg.d)经腹腔注射MPTP共7 d制成PD模型,预防组小鼠按体重40 mg/(kg.d)经腹腔注射PDTC半小时后再经腹腔注射MPTP。观察两组小鼠注射前后行为变化,并采用SABC法检测注射后黑质部NF-κB及酪氨酸羟化酶(TH)的表达情况。结果实验组小鼠表现出PD的典型症状,预防组则无异常行为表现。实验组小鼠黑质部NF-κB阳性表达较预防组显著,并有明显核易位现象,TH阳性神经元显著减少(均P<0.01)。结论NF-κB参与了MPTP PD鼠发病过程,黑质中NF-κB过度激活是MPTP对小鼠造成损害作用的机制之一。预先使用PDTC对MPTP PD鼠起到一定神经保护作用。

Objective To investigate the effects of pyrrolidine dithiocarbamate （PDTC） on the expression of nuclear factor-kappaB （NF-kB） in the substantia nigra of Parkinson disease （PD） mouse model by 1-methyl-4- phenyl-1, 2, 3, 6 tetrahydropyridine （MPTP）. Methods With C57/BL mice, MPTP was administered at a dose of 30 mg/kg i. p. at 24-hour intervals for seven doses in the test group mice in order to make PD models. Mice in the prevention group were pre-treated with MPTP as in the test group, after half an hour then treated with PDTC administered at a dose of 40 mg/kg i. p. at 24-hour intervals also for seven doses. Before administered and after administered for seven doses, mice in the two groups were observed their behaviors. Then immunohistochemistry by SABC was performed on serial sections of the substantia nigra for NF-kB and tyrosine hydroxylase （TH）. Results All mice in the test group manifested typical symptoms of PD. All mice in the prevention group little symptoms of PD manifested, just the same as usual. There were more distinct expression of positive NF-kB and phenomenon of dislocation into cell nucleus in the substantia nigra of the test group than those of the prevention group. Immunoreactivities of NF-kB and TH in the substantia nigra of the test group had significant difference in statistics from those of the prevention group （P〈0. 01）. Conclusions NF-kB may participated in the course of MPTP induced PD, excess activated NF-kB in the substantia nigra may be involved in damage mechanism induced by MPTP. PDTC might play a role of nerve safeguard＇ s effects on MPTP induced PD, if PDTC was preadopted.