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美金刚对 STZ 诱导的阿尔茨海默病大鼠 Bace1-as 和 Bace1 基因表达的影响。

Effect of memantine on expression of Bace1-as and Bace1 genes in STZ-induced Alzheimeric rats.

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Memory and Behavioral Neurology Department (MBND), Roozbeh Hospital, Tehran, Iran.

出版信息

Mol Biol Rep. 2020 Aug;47(8):5737-5745. doi: 10.1007/s11033-020-05629-7. Epub 2020 Jul 9.

Abstract

Recent studies have showed that the long non-coding RNAs (lncRNAs) expression is dysregulated in different neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the effects of memantine on the level of Bace1-as and Bace1 genes' expression in streptozotocin (STZ)-induced Alzheimer's and memantine treated rats were investigated. The male Wistar rats were randomly divided into four groups: 1-Normal control, 2-Sham-operated control, 3- Alzheimer'scontrol rats (ICV-STZ), 4-Experimental group rats treated by memantine in a dose of 30 mg/kg/day for 28 days in ICV-STZ rats. The expression of Bace1-as and Bace1 genes was measured by quantitative-PCR in the brain and blood tissues. ELISA was used to analyze Bace1 and Aβ proteins. Expression of Bace1-as was significantly increased in the brain and blood tissues of the experimental group (p = 0.032 and p = 0.034, respectively). The expression of Bace1 gene showed no significant changes in the brain. Furthermore, the ELISA analysis revealed that Bace1 protein was significantly increased in the plasma of the Alzheimer's control group (p = 0.000) and in the brain tissue of the experimental group (p = 0.000). Additionally, Aβ levels had no significant changes between all groups studied. The Bace1 protein may be used as a prognostic biomarker in plasma, or before using memantine as a treatment. Furthermore, Bace1-as gene expression may play a role in monitoring the progression of AD.

摘要

最近的研究表明,长链非编码 RNA(lncRNA)在不同的神经退行性疾病(如阿尔茨海默病(AD))中的表达失调。在本研究中,研究了美金刚对链脲佐菌素(STZ)诱导的阿尔茨海默病和接受美金刚治疗的大鼠中 Bace1-as 和 Bace1 基因表达水平的影响。雄性 Wistar 大鼠随机分为四组:1-正常对照组,2-假手术对照组,3-阿尔茨海默病对照组(ICV-STZ),4-实验组大鼠用美金刚治疗,剂量为 30mg/kg/天,共 28 天,在 ICV-STZ 大鼠中。通过定量 PCR 测量大脑和血液组织中 Bace1-as 和 Bace1 基因的表达。ELISA 用于分析 Bace1 和 Aβ 蛋白。Bace1-as 的表达在实验组的大脑和血液组织中显着增加(p=0.032 和 p=0.034)。Bace1 基因在大脑中的表达没有显着变化。此外,ELISA 分析表明,Bace1 蛋白在阿尔茨海默病对照组的血浆中显着增加(p=0.000),在实验组的脑组织中也显着增加(p=0.000)。此外,所有研究组之间的 Aβ 水平没有显着变化。Bace1 蛋白可作为血浆中的预后生物标志物,或在使用美金刚作为治疗之前使用。此外,Bace1-as 基因表达可能在监测 AD 进展中发挥作用。

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