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氧化应激、炎症环境与代谢综合征复发性植入失败患者的 microRNA 调控

Oxidative stress, inflammatory settings, and microRNA regulation in the recurrent implantation failure patients with metabolic syndrome.

机构信息

Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Am J Reprod Immunol. 2019 Oct;82(4):e13170. doi: 10.1111/aji.13170. Epub 2019 Aug 11.

DOI:10.1111/aji.13170
PMID:31310689
Abstract

PROBLEM

Increased oxidative stress (OS) and inflammatory factors in metabolic syndrome (MS) patients are considered as risk factors for recurrent implantation failure (RIF). The aim of this study was to investigate OS markers, inflammatory factors, related microRNAs (miRNA) expression, and cytokine and transcription factors RNA expression.

METHOD OF STUDY

We evaluated the frequency of helper T (Th) 17 and regulatory T (Treg) cells in recurrent implantation failure (RIF) women with or without MS. miRNA expression, an inflammatory cytokine, and transcription factors were measured by real-time PCR. The level of interleukin (IL)-1β, IL-6, IL-17, tumour necrosis factor-alpha (TNF-alpha) and chemokine (C-C motif) ligand 2 (CCL-2), and C-X-C motif chemokine ligand 8 (CXCL-8) were measured by enzyme-linked immunosorbent assay (ELISA). OS markers were evaluated by spectrophotometric assay. Th17 and Treg cell frequencies were determined by flow cytometry.

RESULTS

The expression of AP1, NF-κB, FOXP3, miRNA-21; serum or plasma level of OS markers (ie, nitric oxide, total oxidant status, and myeloperoxidase); serum level of inflammatory factors (ie, IL1-β, IL-6, IL-17, TNF-alpha, CXCL-8, and CCL-2); and frequency of Th17 cells were increased in RIF-MS patients in comparison with RIF women without MS (RIF-NMS) and control group. The expression of miRNA-223 and 146a, antioxidant enzymes, namely superoxide dismutase (SOD) and catalase (CAT), and frequency of Treg also declined in RIF-MS patients.

CONCLUSION

Overall, our findings suggest that MS in RIF patients causes increased inflammatory factors and OS, which in turn leads to implantation failure.

摘要

问题

代谢综合征(MS)患者的氧化应激(OS)和炎症因子增加被认为是复发性着床失败(RIF)的危险因素。本研究旨在探讨 OS 标志物、炎症因子、相关 microRNA(miRNA)表达以及细胞因子和转录因子 RNA 表达。

方法

我们评估了伴有或不伴有 MS 的 RIF 女性中辅助性 T(Th)17 和调节性 T(Treg)细胞的频率。通过实时 PCR 测定 miRNA 表达、炎症细胞因子和转录因子。通过酶联免疫吸附试验(ELISA)测定白细胞介素(IL)-1β、IL-6、IL-17、肿瘤坏死因子-α(TNF-α)和趋化因子(C-C 基序)配体 2(CCL-2)以及 C-X-C 基序趋化因子配体 8(CXCL-8)的水平。通过分光光度法评估 OS 标志物。通过流式细胞术测定 Th17 和 Treg 细胞频率。

结果

AP1、NF-κB、FOXP3、miRNA-21 的表达;氧化应激标志物(即一氧化氮、总氧化剂状态和髓过氧化物酶)的血清或血浆水平;炎症因子(即 IL1-β、IL-6、IL-17、TNF-α、CXCL-8 和 CCL-2)的血清水平;以及 Th17 细胞的频率在 RIF-MS 患者中均高于 RIF 无 MS 患者(RIF-NMS)和对照组。miRNA-223 和 146a、抗氧化酶,即超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的表达以及 Treg 的频率在 RIF-MS 患者中也下降。

结论

总的来说,我们的研究结果表明,RIF 患者的 MS 导致炎症因子和 OS 增加,进而导致着床失败。

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