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口服益生菌营养补充剂对营养不良血液透析患者 miR-29a 和 miR-29b 表达及其炎症和肾纤维化相关靶基因的调控作用

Modulation of miR-29a and miR-29b Expression and Their Target Genes Related to Inflammation and Renal Fibrosis by an Oral Nutritional Supplement with Probiotics in Malnourished Hemodialysis Patients.

机构信息

Servicio de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain.

Instituto de Investigación Biomédica de Málaga IBIMA-Plataforma BIONAND, 29009 Málaga, Spain.

出版信息

Int J Mol Sci. 2024 Jan 17;25(2):1132. doi: 10.3390/ijms25021132.

DOI:10.3390/ijms25021132
PMID:38256206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10816158/
Abstract

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS), specifically designed for malnourished (or at risk) hemodialysis patients with a "similar to the Mediterranean diet" pattern, improved caloric-protein intake, nutritional status and biomarkers of inflammation and oxidation. Our aim in this study was to evaluate whether the new ONS, associated with probiotics or not, may produce changes in miRNA's expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We performed a randomized, multicenter, parallel-group trial in malnourished hemodialysis patients with three groups (1: control (C) individualized diet ( = 11); 2: oral nutritional supplement (ONS) + placebo (ONS-PL) ( = 10); and 3: ONS + probiotics (ONS-PR) ( = 10)); the trial was open regarding the intake of ONS or individualized diet recommendations but double-blinded for the intake of probiotics. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for and . expression was decreased in the ONS-PR group compared to baseline in the third month. gene expression was significantly elevated in the ONS-PR group at 3 months in comparison with baseline. expression was significantly increased in the ONS-PL group at the 3-month intervention compared to baseline. The new oral nutritional supplement associated with probiotics increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this oral nutritional supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

摘要

营养不良在慢性肾脏病(CKD)患者中很常见,尤其是那些接受血液透析的患者。最近,我们的研究小组描述了一种新的口服营养补充剂(ONS),专门为患有“类似于地中海饮食”模式的营养不良(或有风险)血液透析患者设计,可以改善热量-蛋白质摄入、营养状况以及炎症和氧化生物标志物。我们的研究目的是评估新的 ONS 是否与益生菌联合使用可以改变营养不良血液透析患者的 miRNA 表达及其靶基因,与个体化饮食建议相比。我们在营养不良的血液透析患者中进行了一项随机、多中心、平行组试验,分为三组(1:对照组(C)个体化饮食(=11);2:口服营养补充剂(ONS)+安慰剂(ONS-PL)(=10);3:ONS+益生菌(ONS-PR)(=10));ONS 或个体化饮食建议的摄入量是开放的,但益生菌的摄入量是双盲的。在基线和 3 个月和 6 个月时,通过 RT-qPCR 分析 miRNA 和基因表达水平。我们观察到,与基线相比,ONS-PR 组的 miR-29a 和 miR-29b 的表达在 3 个月时显著增加,并在第六个月稳定。此外,我们观察到研究组之间的差异,在第三个月时,接受 ONS-PR 的患者的 miR-29b 表达水平高于对照组。关于基因表达水平,我们观察到 ONS-PR 组与对照组相比,在第三个月时 和 的表达水平下降。ONS-PR 组与基线相比,在第三个月时 的表达下降。ONS-PR 组在第三个月时与基线相比, 基因的表达显著升高。ONS-PL 组在第三个月的干预时与基线相比, 的表达显著增加。新型口服营养补充剂联合益生菌可在干预 3 个月后增加 miR-29a 和 miR-29b 的表达水平,调节具有抗炎和抗纤维化作用的靶基因的表达。这项研究强调了这种口服营养补充剂的潜在益处,特别是与益生菌联合使用,对营养不良的慢性肾脏病血液透析患者有益。

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