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在先前一项前瞻性双盲安慰剂对照随机临床试验的子研究中,经过四年的硒和Q干预后,SIRT1浓度升高与10年随访时心血管死亡率降低相关。

Increased SIRT1 Concentration Following Four Years of Selenium and Q Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up-Sub-Study of a Previous Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial.

作者信息

Opstad Trine Baur, Alexander Jan, Aaseth Jan, Larsson Anders, Seljeflot Ingebjørg, Alehagen Urban

机构信息

Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4950, Nydalen, N-0424 Oslo, Norway.

Faculty of Medicine, University of Oslo, N-0370 Oslo, Norway.

出版信息

Antioxidants (Basel). 2023 Mar 21;12(3):759. doi: 10.3390/antiox12030759.

Abstract

: Selenium and coenzyme Q (SeQ) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ intervention on SIRT1 concentration, with potential interactions with microRNAs. : In this sub-study of a prospective double-blind placebo-controlled clinical trial, healthy subjects (mean age 76 years) were randomized to receive an active treatment ( = 165, combined 200 µg/day of Se and 200 mg/day of Q) or a placebo ( = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. : After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), = 0.002, and the differences between the groups were significant ( = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up ( = 25 and = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors ( < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = -0.466, = 0.007). : The increased SIRT1 concentration after the SeQ intervention associated with reduced CV mortality, partly mediated via miR-1303a-3p, suggests that SIRT1 is an additional mediator of the intervention, preventing vascular ageing.

摘要

硒和辅酶Q(SeQ)具有抗氧化和抗炎特性,可能通过沉默调节蛋白1(SIRT1)介导。我们旨在研究SeQ干预对SIRT1浓度的影响,以及与微小RNA的潜在相互作用。

在这项前瞻性双盲安慰剂对照临床试验的子研究中,健康受试者(平均年龄76岁)被随机分为接受活性治疗组(n = 165,联合补充200μg/天的硒和200mg/天的辅酶Q)或安慰剂组(n = 161)。分别采用酶联免疫吸附测定法(ELISA)和聚合酶链反应(PCR)检测SIRT1浓度和微小RNA。

四年后,活性治疗组的SIRT1浓度升高,平均(标准差)为469(436)ng/mL,而安慰剂组为252(162)ng/mL,P < 0.001;安慰剂组的SIRT1浓度降低,为190(186)ng/mL,而之前为269(172)ng/mL,P = 0.002,两组之间的差异具有统计学意义(P = 0.006,校正后)。在10年随访期间发生心血管死亡的患者(活性治疗组和安慰剂组分别为25例和52例),其基线SIRT1浓度显著低于幸存者(P < 0.001)。在干预期间,miR-130a-3p显著下调,且在基线时与SIRT1呈负相关(r = -0.466,P = 0.007)。

SeQ干预后SIRT1浓度升高与心血管死亡率降低相关,部分通过miR-1303a-3p介导,这表明SIRT1是该干预的另一种介导因子,可预防血管衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0fb/10045001/a25766b19613/antioxidants-12-00759-g001.jpg

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