BDNF在Parkinson病小鼠的表达及丙戊酸盐对其影响的研究

为观察Parkinson病(PD)小鼠脑源性神经营养因子(BDNF)含量的变化及丙戊酸盐(valproate,VPA)对BDNF表达的影响,探讨VPA对PD病神经元的保护作用,本研究采用C57BL/6小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy1-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)法建立PD模型。小鼠随机分为4组:盐水对照组(NS+NS)、模型组(NS+MPTP)、模型给药组(VPA+MPTP)和单独给药组(VPA+NS)。MPTP造模方法为每日颈部皮下注射MPTP(20 mg/kg),连续8 d。VPA在MPTP造模前1 d开始给药(400 mg/kg,i.p.),共14 d。单独给药组给予VPA,同时用等量的生理盐水代替MPTP。盐水对照组仅给予等量的生理盐水。采用原位分子杂交方法观察BDNF的表达,并对检测部位恒定视野内BDNF的阳性细胞进行灰度扫描和统计学分析。结果显示:与盐水对照组相比,模型组、模型给药组和单独给药组小鼠纹状体、海马、皮质内BDNF的表达均增强。该结果提示,PD小鼠神经元内BDNF增多,可能有利于受损神经元的修复;丙戊酸盐可能通过促进BDNF的表达而保护神经元。

The expression of BDNF and the effect of valproate on Parkinson''s disease mice

To investigate the expression of brain-derived neurotrophic factor(BDNF) in mice with Parkinson's disease(PD),and to study the neuroprotective effects of valproate(VPA),the PD model was established by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) to C57BL/6 mice.The mice were randomly divided into four groups,including normal saline(NS) NS group,NS MPTP group,VPA MPTP group and VPA NS group.MPTP(20 mg/kg,s.c.) was continuously injected for 8 days to make PD model(NS was used to replace MPTP in control).Since one day prior to MPTP application,VPA(400 mg/kg,i.p.) was continuouly applied for 14 days.In situ hybridization was used to observe the levels of BDNF thereafter.BDNF positive neurons were scanned and their gray value was statistically analyzed.The results showed that the expression of BDNF in the striatum,hippocampus,cerebral cortex was significantly increased in NS MPTP group,VPA MPTP group and VPA NS group compared to NS NS group,respectively,suggesting that BDNF may be involved in the neuroprotection and repairment of injured tissue and VPA exerts function through increased expression of BDNF.