中性粒细胞胞外诱捕网在新生儿急性呼吸窘迫综合征中的表达及意义

Levels of neutrophil extracellular traps in neonates with acute respiratory distress syndrome

摘要:

目的 动态观察中性粒细胞胞外诱捕网（neutrophil extracellular traps，NETs）的标记物游离DNA（cell free-DNA，cf-DNA）在新生儿急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）中的变化，并评估其与ARDS病情严重程度及早期诊断的关系。方法 前瞻性纳入2021年1月—2022年6月入住江苏大学附属医院诊断为ARDS的新生儿作为研究组（ARDS组），根据氧指数（oxygen index，OI）分为轻度ARDS组（4≤OI<8）、中度ARDS组（8≤OI<16）及重度ARDS组（OI≥16）。对照组选自同期在该院新生儿科观察的黄疸新生儿，均无引起新生儿黄疸的病理性因素。ARDS组在入院后第1、3、7天采集外周血标本，对照组在入院时采集外周血标本。采用荧光酶标仪检测血清cf-DNA水平；采用酶联免疫吸附法检测血清白细胞介素6（interleukin 6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平。采用Pearson相关分析法评估血清cf-DNA水平与血清IL-6和TNF-α水平的相关性。结果 ARDS组共纳入50例患儿，其中轻度ARDS 15例，中度ARDS 25例，重度ARDS 10例；对照组纳入25例新生儿。与对照组相比，不同病情程度的ARDS各组血清cf-DNA、IL-6、TNF-α水平显著增加（P<0.05）。与轻度ARDS组相比，中度及重度ARDS组血清cf-DNA、IL-6、TNF-α水平显著增加（P<0.05），重度ARDS组增加更为明显（P<0.05）。与入院后第1天相比，ARDS各组血清cf-DNA、IL-6、TNF-α水平在入院后第3天显著增加，而第7天显著下降（P<0.05）。Pearson相关分析显示，在50例ARDS新生儿中，血清cf-DNA水平与血清IL-6及TNF-α水平均呈正相关（P<0.05）。结论 ARDS新生儿存在NETs过量表达，动态监测cf-DNA水平在评估新生儿ARDS病情严重程度及早期诊断中有一定临床价值。

Abstract:

Objective To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS.Methods The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively). The control group was selected from jaundice neonates who were observed in the neonatal department of the hospital during the same period, and they had no pathological factors causing neonatal jaundice. Peripheral blood samples were collected on day 1, day 3, and day 7 after admission for the ARDS group, and on the day of admission for the control group. Serum cf-DNA levels were measured using a fluorescence enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using enzyme-linked immunosorbent assay. A Pearson correlation analysis was used to evaluate the correlation of serum cf-DNA levels with serum IL-6 and TNF-α levels.Results A total of 50 neonates were enrolled in the ARDS group, including 15 neonates with mild ARDS, 25 with moderate ARDS, and 10 with severe ARDS. Twenty-five neonates were enrolled in the control group. Compared with the control group, the serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased (P<0.05). Compared with the mild ARDS group, the serum levels of cf-DNA, IL-6, and TNF-α in the moderate and severe ARDS groups were significantly increased (P<0.05), and the increase was more significant in the severe ARDS group (P<0.05). The serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased on day 3 after admission and significantly decreased on day 7 after admission compared with those on day 1 after admission (P<0.05). The Pearson correlation analysis showed that there was a positive correlation between serum cf-DNA levels and IL-6 levels as well as TNF-α levels in 50 neonates with ARDS (P<0.05).Conclusions There is an excessive expression of NETs in neonates with ARDS, and dynamic monitoring of serum cf-DNA levels has certain clinical value in evaluating the severity and early diagnosis of ARDS in neonates.