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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。
In order to observe the changes of brain-derived neurotrophic factor (BDNF) in mice with Parkinson’s disease (PD) and the effect of valproate (VPA) on the expression of BDNF, and to explore the protective effect of VPA on neurons in PD, The C57BL / 6 mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) method was used to establish PD model. The mice were randomly divided into 4 groups: saline control group (NS + NS), model group (NS + MPTP), model administration group (VPA + MPTP) and single administration group (VPA + NS). The MPTP model was subcutaneously injected with MPTP (20 mg / kg) daily for 8 days. VPA was administered 1 day before MPTP (400 mg / kg, i.p.) for 14 days. VPA was given to the single administration group while an equivalent amount of normal saline was used instead of MPTP. Saline control group was given only the same amount of saline. The in situ hybridization was used to observe the expression of BDNF. The positive cells of BDNF in the constant field of vision were scanned by gray scale and analyzed statistically. The results showed that BDNF expression in striatum, hippocampus and cortex increased in model group, model group and single administration group compared with saline control group. The results suggest that BDNF increased in neurons of PD mice may be beneficial to the repair of damaged neurons; Valproate may protect neurons by promoting the expression of BDNF.