米屈肼对帕金森病大鼠模型蛋白表达的调节作用。

Mildronate as a regulator of protein expression in a rat model of Parkinson's disease.

机构信息

Department of Pathology, University of Latvia, Riga. Latvia.

出版信息

Medicina (Kaunas). 2011;47(10):552-9.

Abstract

BACKGROUND

Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson's disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM).

MATERIAL AND METHODS

PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by western blot assay.

RESULTS

6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values.

CONCLUSION

The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.

摘要

背景

米力农（二水合 3-[2,2,2-三甲基肼基]丙酸盐）传统上是一种著名的心脏保护药物。然而，我们最近的研究令人信服地证明了它的神经保护特性。本研究的目的是评估米力农对帕金森病（PD）大鼠模型中涉及黑质纹状体多巴胺能神经元分化和存活的蛋白质表达的影响。使用了以下生物标志物：热休克蛋白 70（Hsp70，一种分子伴侣）、胶质细胞系衍生的神经生长因子（GDNF，一种促进神经元分化、再生和存活的生长因子）和神经细胞黏附分子（NCAM）。

材料和方法

通过 6-羟多巴胺（6-OHDA）单侧纹状体注射在大鼠中建立 PD 模型。米力农以 10、20 和 50mg/kg 的剂量腹腔注射，在 6-OHDA 注射前 2 周给药。在停止米力农注射后第 28 天，取出大鼠大脑。通过免疫组织化学和 Western blot 分析评估生物标志物的表达。

结果

6-OHDA 降低了损伤纹状体和黑质中 Hsp70 和 GDNF 的表达，而在米力农预处理（20 和 50mg/kg）大鼠中，Hsp70 和 GDNF 的表达接近对照组值。6-OHDA 还降低了纹状体中 NCAM 的表达，而米力农（50mg/kg）预处理完全保护了它。相比之下，6-OHDA 在黑质中增加了 NCAM 的表达，而米力农预处理（20 和 50mg/kg）使 6-OHDA 诱导的 NCAM 过表达接近对照组值。