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瑞舒伐他汀可降低血脂异常阿尔茨海默病患者的总tau 血清水平并增加 miR-124-3p 的表达:一项历史性队列研究。

Rosuvastatin attenuates total-tau serum levels and increases expression of miR-124-3p in dyslipidemic Alzheimer's patients: a historic cohort study.

机构信息

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran.

Cellular and Molecular Research Center, Research Institute for Non-communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.

出版信息

Metab Brain Dis. 2024 Aug;39(6):1201-1211. doi: 10.1007/s11011-024-01371-2. Epub 2024 Jun 19.

DOI:10.1007/s11011-024-01371-2
PMID:38896205
Abstract

microRNAs are candidate diagnostic biomarkers for Alzheimer's disease. This study aimed to compare Silymarin with Rosuvastatin and placebo on total-Tau protein level and expression levels of microRNAs and TGF-β and COX-2 in Alzheimer's patients with secondary dyslipidemia. 36 mild AD patients with dyslipidemia were divided into three groups of 12. The first group received silymarin (140mg), the second group received placebo (140mg), and the third group recieved Rosuvastatin (10mg). Tablets were administered three times a day for Six months. The blood samples of the patients were collected before and after the intervention and the serum was separated. Using the RT-qPCR method, the expression levels of miR-124-3p and miR-125b-5p were assessed, and the serum levels of total-Tau, TGF-β, and COX-2 enzyme were measured using the ELISA method. Data were analyzed with SPSS software. In this study, the level of Δtotal-Tau was significantly lower in the Rosuvastatin group compared to the placebo (P = 0.038). Also, a significant reduction in the level of ΔTGF-β was observed in the Silymarin to Rosuvastatin group (p = 0.046) and ΔmiR-124-3p was significantly increased in the Rosuvastatin compared to the placebo group (p = 0.044). Rosuvastatin outperformed silymarin in decreasing Δtotal-Tau serum levels and enhancing expression of ΔmiR-124-3p, attributed to Rosuvastatin's capacity to lower cholesterol levels and inflammation concurrently. Conversely, silymarin was more effective than Rosuvastatin in reducing levels of ΔTGF-β. Serum miR-124-3p could serve as a promising diagnostic biomarker and a new therapeutic focus in AD.

摘要

microRNAs 是阿尔茨海默病的候选诊断生物标志物。本研究旨在比较水飞蓟素、瑞舒伐他汀和安慰剂对伴有继发性血脂异常的阿尔茨海默病患者总 Tau 蛋白水平及 microRNAs、TGF-β 和 COX-2 表达水平的影响。将 36 例伴有血脂异常的轻度 AD 患者分为三组,每组 12 例。第一组给予水飞蓟素(140mg),第二组给予安慰剂(140mg),第三组给予瑞舒伐他汀(10mg)。三组患者均每日给药 3 次,疗程为 6 个月。在干预前后采集患者的血样,分离血清。采用 RT-qPCR 法检测 miR-124-3p 和 miR-125b-5p 的表达水平,采用 ELISA 法检测血清总 Tau、TGF-β 和 COX-2 酶水平。数据采用 SPSS 软件进行分析。本研究中,与安慰剂组相比,瑞舒伐他汀组的总 Tau 水平明显降低(P=0.038)。此外,水飞蓟素组与瑞舒伐他汀组的 TGF-β 水平明显降低(P=0.046),瑞舒伐他汀组的 miR-124-3p 水平明显升高(P=0.044)。与水飞蓟素相比,瑞舒伐他汀能更显著降低总 Tau 血清水平并增强 miR-124-3p 的表达,这归因于瑞舒伐他汀同时降低胆固醇和炎症的能力。相反,水飞蓟素在降低 TGF-β 水平方面比瑞舒伐他汀更有效。血清 miR-124-3p 可能成为 AD 有前途的诊断生物标志物和新的治疗靶点。

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