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阿尔茨海默病患者血清和脑脊液中 NEAT1 和 miR-27a-3p 的表达关系及意义。

Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer's disease.

机构信息

Department of Clinical Laboratory, Tianjin Fifth Central Hospital, 41 Zhejiang Road, Tianjin, 300450, People's Republic of China.

General Surgery, Tianjin Fifth Central Hospital, Tianjin, 300450, People's Republic of China.

出版信息

BMC Neurol. 2022 Jun 3;22(1):203. doi: 10.1186/s12883-022-02728-9.

Abstract

OBJECTIVE

To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer's disease (AD).

METHODS

Sixty-six AD patients received by the Department of Neurology of our hospital from October 2019 to September 2021 were gathered, according to the Clinical Dementia Rating Scale (CDR) score, they were grouped into mild group (≤1 point, n = 41) and moderate-to-severe group (> 1 point, n = 25). Another 32 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general materials on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with MMSE and MoCA scores;Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels.

RESULTS

The MMSE score, MoCA score, serum miR-27a-3p level, cerebrospinal fluid miR-27a-3p, Aβ42 levels and Aβ42/Aβ40 ratio of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05);the serum NEAT1 level, SUVR, and cerebrospinal fluid NEAT1 and BACE1 levels were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 (r = 0.350, 0.606, 0.341, all P < 0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level (r = 0.695, P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level (r = - 0.521, - 0.447, both P < 0.05).

CONCLUSIONS

The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

摘要

目的

探讨长链非编码 RNA 核富集丰富转录物 1(LncRNA NEAT1)和 miR-27a-3p 在阿尔茨海默病(AD)患者血清和脑脊液中的表达关系及意义。

方法

收集 2019 年 10 月至 2021 年 9 月我院神经内科收治的 66 例 AD 患者,根据临床痴呆评定量表(CDR)评分,将其分为轻度组(≤1 分,n = 41)和中重度组(>1 分,n = 25)。另选取 32 例门诊体检人员的血清和脑脊液样本作为对照组。记录所有受试者的一般资料并进行认知评估;实时定量 PCR 检测血清和脑脊液中 miR-27a-3p 和 NEAT1 的表达水平;酶联免疫吸附试验检测脑脊液中β-淀粉样前体蛋白裂解酶 1(BACE1)、β-淀粉样蛋白(Aβ)40 和 Aβ42 的蛋白水平;Spearman 法分析血清 miR-27a-3p 和 NEAT1 水平与 MMSE 和 MoCA 评分的相关性;Pearson 法分析血清 miR-27a-3p 和 NEAT1 水平与 Aβ 沉积标准摄取值比(SUVR)以及脑脊液 miR-27a-3p、NEAT1、BACE1、Aβ42 和 Aβ40 水平的相关性。

结果

AD 患者轻度组和中重度组的 MMSE 评分、MoCA 评分、血清 miR-27a-3p 水平、脑脊液 miR-27a-3p、Aβ42 水平和 Aβ42/Aβ40 比值均低于对照组,且中重度组低于轻度组(均 P < 0.05);血清 NEAT1 水平、SUVR 及脑脊液 NEAT1 和 BACE1 水平均高于对照组,且中重度组高于轻度组(均 P < 0.05)。AD 患者血清 NEAT1 水平与 SUVR、脑脊液 NEAT1 和 BACE1 呈正相关(r = 0.350、0.606、0.341,均 P < 0.05);血清 miR-27a-3p 水平与脑脊液 miR-27a-3p 水平呈正相关(r = 0.695,P < 0.05),与 SUVR 和脑脊液 BACE1 水平呈负相关(r = - 0.521、- 0.447,均 P < 0.05)。

结论

AD 患者血清和脑脊液中 NEAT1 和 miR-27a-3p 的表达趋势一致,均表现为 NEAT1 水平升高,miR-27a-3p 水平降低。两者呈负相关,与 AD 患者脑内 Aβ 沉积程度有关,参与 AD 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a950/9164380/ef4e56ad93b3/12883_2022_2728_Fig1_HTML.jpg

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