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阿尔茨海默病患者大脑不同区域中 SIRT1 和 SOD-1 的表达降低及其相关性。

Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in various regions of the brains of patients with Alzheimer's disease.

机构信息

Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guizhou Medical University, Guiyang, China.

出版信息

J Clin Pathol. 2018 Dec;71(12):1090-1099. doi: 10.1136/jclinpath-2018-205320. Epub 2018 Sep 5.

DOI:10.1136/jclinpath-2018-205320
PMID:30185534
Abstract

AIMS

This study was designed to explore the expression and distribution of silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in various regions of the brains of patients with Alzheimer's disease (AD), as well as to assess potential correlations between the levels of these proteins and also between these proteins and the Braak stage of AD.

METHODS

In the temporal and frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age-matched control subjects, expression of SIRT1 and SOD-1, together with histopathology, were assessed by immunohistochemical and immunofluorescent stainings. Relationships between variables were examined with the Pearson correlation test.

RESULTS

The numbers of both SIRT1-positive and SOD-1-positive neurons and integrated optical density of immunohistochemical staining for these proteins in the temporal and frontal cortices, and hippocampus of patients with AD were significantly decreased than those in corresponding controls. In the case of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1 were observed in granule cells, with no significant difference between AD and the control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in neurons in all regions of the AD brains investigated except for the cerebellum.

CONCLUSIONS

These findings indicate that the reduced level of SIRT1 in the brains of patients with AD may be related to the decline in SOD-1 and neuropathological changes of this disorder.

摘要

目的

本研究旨在探讨沉默信息调节因子 1(SIRT1)和超氧化物歧化酶 1(SOD-1)在阿尔茨海默病(AD)患者大脑不同区域的表达和分布情况,并评估这些蛋白质的水平与 AD 的 Braak 分期之间以及这些蛋白质之间的潜在相关性。

方法

对 10 例 AD 患者和 10 例年龄匹配的对照组患者的颞叶和额叶皮质、海马和小脑组织中 SIRT1 和 SOD-1 的表达情况,通过免疫组织化学和免疫荧光染色进行评估。采用 Pearson 相关检验分析变量之间的关系。

结果

AD 患者颞叶和额叶皮质及海马中 SIRT1 阳性和 SOD-1 阳性神经元的数量以及免疫组化染色的积分光密度均显著低于对照组。小脑中 SIRT1 表达微弱,SOD-1 表达明显,AD 组与对照组之间无显著差异。有趣的是,除小脑外,AD 患者大脑各区域神经元中 SIRT1 与 SOD-1 之间的蛋白水平以及 SIRT1 或 SOD-1 水平与 Braak 分期之间均呈显著相关性。

结论

这些发现表明,AD 患者大脑中 SIRT1 水平降低可能与 SOD-1 下降以及该疾病的神经病理学变化有关。

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