关键词: 阿尔茨海默病, 富硒食物, β淀粉样蛋白, 同型半胱氨酸, 微管相关蛋白

Abstract:

Objective To detect the biological markers related to Alzheimer’s disease（AD） in the peripheral blood of AD patients， and to explore the activities and levels of the antioxidant function indexes and the expressions of related genes and proteins in the blood of AD patients and the changes after intervention of selenium-rich food. Methods The Mini-Mental State Examination （MMSE） combined with electroencephalogram or brain CT and clinician diagnosis were used for screening AD. Fifty-six elderly patients with AD aged 75-90 years old were selected. Among them，28 cases were selected as normal diet group for AD （AD group）， and 28 cases were selected as dietary selenium intervention group （Se-AD group）. The patients in Se-AD group were given daily dietary selenium supplementation （increaseing dietary selenium by 15-20 μg per day） for 3 months.Meanwhile， 30 people with the same age were selected as healthy control group. The activities of serum superoxide dismutase（SOD）， cholinesterase（CHE）， and glutathione peroxidase （GSH-Px） and the levels of serum malondialdehyde （MDA）， homocysteine （Hcy）， and nitric oxide （NO） as well as reagent kit the levels of serum β-amyloid protein （Aβ）， and microtubule-associated protein （Tau） and phosphorylated microtubule-associated protein（p-Tau） of the subjects in various groups were detected by and enzyme-linked immunosorbent assay（ELISA） method； the expression levels of apolipoprotein E4 （ApoE4）， presenilin 1 （PS1）， presenilin 2 （PS2）， cysteinyl aspartate specific proteinase 3 （Caspase3）， sorting associated protein receptor 1 （SORL1）， β-site amyloid precursor protein cleaving enzyme 1 （BACE1）， hypoxia-inducible factor 1 （HIF1）， nuclear factor-kappa B （NF-κB）， β-amyloid precursor protein （APP）， protein kinase C （PKC）， and Aβ mRNA in peripheral blood of the subjects various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） method. Results Compared with healthy control group， the serum SOD activities of the patients in Se-AD group and AD group were significantly decreased （P<0.05）， while serum CHE activity and the levels of MDA and Hcy were significantly increased （P<0.05）；the serum GSH-Px activity of the patients in AD group was significantly decreased （P< 0.05）， and the level of NO was significantly increased （P<0.05）. Compared with Se-AD group， serum CHE activity and the level of Hcy of the patients in AD group were significantly increased （P<0.05）. The expression levels of ApoE4， PS1， Caspase3， BACE1， NF-κB and APP mRNA of the patients in Se-AD group and AD group were significantly increased （P<0.05）， and the expression levels of PKC mRNA were significantly decreased （P<0.05）； the expression level of PS2 mRNA of the patients in AD group was significantly increased （P<0.05）， and the expression levels of Aβ mRNA of the patients in Se-AD group and AD group were significantly increased （P<0.05）. Conclusion The activities of serum SOD， GSH-Px and CHE and the levels of MDA， Hcy and NO， the levels of Aβ， Tau and p-Tau proteins，and the expression levels of ApoE4， PS1， Caspase3， BACE1， NF-κB， PKC， PS2， Aβ and APP mRNA in peripheral blood of the AD patients may vary and can be used for clinical diagnosis of the AD patients．Selenium-rich food can improve AD to some extent， and its mechanism is related to reducing the oxidative damage of brain tissue and decreasing the expression of AD related genes PS2 and Aβ．

Key words: Alzheimer’s disease, Selenium-rich food, β-amyloid protein, Homocysteine, Microtubule-associated protein