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早产中细胞外DNA水平和细胞因子谱:一项队列研究

Extracellular DNA levels and cytokine profiles in preterm birth: a cohort study.

作者信息

Krasnyi Aleksey M, Sadekova Alsu A, Vtorushina Valentina V, Кan Natalia E, Tyutyunnik Victor L, Krechetova Lyubov V

机构信息

National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Ac.Oparina str. 4, Moscow, Russia, 117997.

I. M. Sechenov First Moscow State Medical UniversityMinistry of Healthcare of Russian Federation, B. Pirogovskaya str. 2-4, Moscow, Russia, 119991.

出版信息

Arch Gynecol Obstet. 2022 Nov;306(5):1495-1502. doi: 10.1007/s00404-022-06456-w. Epub 2022 Feb 26.

DOI:10.1007/s00404-022-06456-w
PMID:35218368
Abstract

PURPOSE

The content of eight different cytokines, cell-free DNA (cfDNA) and cell-free fetal DNA (cffDNA) in women's plasma during preterm birth (PB) was studied. The purpose of this study was to identify the relationships between the investigated factors and determine their prognostic significance.

METHODS

Venous blood samples were collected from 45 women with PB and 35 women with full-term labor at 22-31 and 32-36 weeks of gestation, as well as from 17 women during labor at 39-40 weeks of gestation. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α cytokines in peripheral blood plasma was measured by multiplex method. The level of cfDNA and cffDNA was evaluated using PCR analysis.

RESULTS

It was found that, the level of IL-6, IL-8 and cfDNA in the blood was significantly increased in women with PB at 22-31 weeks of gestation (p = 0.044, p = 0.001, p < 0.001) and 32-36 weeks of gestation (p = 0.025, p = 0.001, p = 0.002) compared to women with physiological pregnancy at the same terms. The level of cffDNA (p = 0.014) was significantly increased in women with PB at 32-36 weeks of gestation. The IL-8 content had a significant correlation with the cfDNA level in women with PB at all stages of labor and with the cffDNA level in the group who gave birth at 32-36 weeks of gestation. There was no correlation between IL-8, cfDNA and cffDNA, but there was consistency with other cytokines at all studied terms and during delivery in the term-delivery group.

CONCLUSION

The results of the study suggest that cfDNA is a potential marker of PB and show that the aberrant relationship between cfDNA and IL-8 may be important in the genesis of PB.

摘要

目的

研究早产(PB)妇女血浆中8种不同细胞因子、游离DNA(cfDNA)和游离胎儿DNA(cffDNA)的含量。本研究的目的是确定所研究因素之间的关系,并确定它们的预后意义。

方法

在妊娠22 - 31周和32 - 36周时,从45例早产妇女和35例足月分娩妇女中采集静脉血样本,以及在妊娠39 - 40周分娩时从17例妇女中采集样本。采用多重方法检测外周血血浆中白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)细胞因子的浓度。使用聚合酶链反应(PCR)分析评估cfDNA和cffDNA的水平。

结果

发现,与同期生理妊娠妇女相比,妊娠22 - 31周(p = 0.044,p = 0.001,p < 0.001)和32 - 36周(p = 0.025,p = 0.001,p = 0.002)的早产妇女血液中IL-6、IL-8和cfDNA水平显著升高。妊娠32 - 36周早产妇女的cffDNA水平(p = 0.014)显著升高。在分娩各阶段,早产妇女的IL-8含量与cfDNA水平以及妊娠32 - 36周分娩组的cffDNA水平均存在显著相关性。IL-8、cfDNA和cffDNA之间无相关性,但在所有研究孕周和足月分娩组分娩期间,与其他细胞因子存在一致性。

结论

研究结果表明cfDNA是早产的潜在标志物,并表明cfDNA与IL-8之间的异常关系可能在早产发生中起重要作用。

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