背景:在组织液中的miRNA的释放显著推荐其用作老年患者轻度认知障碍(MCI)的进展和发病机制的非侵入性诊断生物标志物。
目的:循环miRNAs在MCI发病机制中的潜在作用及其与细胞氧化应激的关系,凋亡,和流通的BDNF,Sirtuin1(SIRT1),在患有MCI的老年人中评估了二肽基肽酶-4(DPP4)。
方法:本研究共招募150名65.4±3.7岁的受试者。将参与者分为两组:健康正常(n=80)和MCI(n=70)。进行实时PCR分析以估计miRNA的相对表达;miR-124a,miR-483-5p,miR-142-3p,和miR-125b,和凋亡相关基因Bax,MCI和对照受试者血清中的Bcl-2和caspase-3。此外,氧化应激参数;MDA,NO,SOD,和CAT;以及血浆DPP4活性,BDNF,用比色法估计SIRT1水平。
结果:与对照组相比,MCI患者血清中miR-124a和miR-483-5p水平显著升高,miR-142-3p和miR-125b水平显著降低。表达的miRNAs与严重的认知衰退显著相关,通过MMSE测量,MoCA,ADL,和记忆分数。Bax的表达,与对照组相比,MCI受试者的caspase-3凋亡诱导基因显着增加,Bcl-2抗凋亡基因显着降低。此外,血浆MDA水平,NO,DPP4活性显著增加,和SOD的水平,CAT,BDNF,与对照组相比,MCI受试者和SIRT1显著降低。表达的miRNAs与NO呈正相关,MDA,DPP4活性,BDNF,和SIRT-1,与CAT的水平呈负相关,SOD,Bcl-2,Bax,和caspase-3基因.
结论:循环miR-124a,miR-483-5p,miR-142-3p,和miR-125b与严重的认知能力下降显著相关,细胞氧化应激,MCI患者的细胞凋亡。因此,它可能是具有高诊断性能的MCI诊断的潜在非侵入性生物标志物。
BACKGROUND: The release of miRNAs in tissue fluids significantly recommends its use as non-invasive diagnostic biomarkers for the progression and pathogenesis of mild cognitive impairment (MCI) in aged patients.
OBJECTIVE: The potential role of circulated miRNAs in the pathogenesis of MCI and its association with cellular oxidative stress, apoptosis, and circulated BDNF, Sirtuin 1 (SIRT1), and dipeptidyl peptidase-4 (DPP4) were evaluated in older adults with MCI.
METHODS: A total of 150 subjects aged 65.4±3.7 years were recruited in this
study. The participants were classified into two groups: healthy normal (n=80) and MCI (n=70). Real-time PCR analysis was performed to estimate the relative expression of miRNAs; miR-124a, miR-483-5p, miR-142-3p, and miR-125b, and apoptotic-related genes Bax, Bcl-2, and caspase-3 in the sera of MCI and control subjects. In addition, oxidative stress parameters; MDA, NO, SOD, and CAT; as well as plasma DPP4 activity, BDNF, SIRT1 levels were colorimetrically estimated.
RESULTS: The levels of miR-124a and miR-483-5p significantly increased and miR-142-3p and miR-125b significantly reduced in the serum of MCI patients compared to controls. The expressed miRNAs significantly correlated with severe cognitive decline, measured by MMSE, MoCA, ADL, and memory scores. The expression of Bax, and caspase-3 apoptotic inducing genes significantly increased and Bcl-2 antiapoptotic gene significantly reduced in MCI subjects compared to controls. In addition, the plasma levels of MDA, NO, and DPP4 activity significantly increased, and the levels of SOD, CAT, BDNF, and SIRT1 significantly reduced in MCI subjects compared to controls. The expressed miRNAs correlated positively with NO, MDA, DPP4 activity, BDNF, and SIRT-1, and negatively with the levels of CAT, SOD, Bcl-2, Bax, and caspase-3 genes.
CONCLUSIONS: Circulating miR-124a, miR-483-5p, miR-142-3p, and miR-125b significantly associated with severe cognitive decline, cellular oxidative stress, and apoptosis in patients with MCI. Thus, it could be potential non-invasive biomarkers for the diagnosis of MCI with high diagnostic performance.