MicroRNA-181a、SIRT1水平与新生儿急性呼吸窘迫综合征严重程度及预后的相关性

Relationship of serum microRNA-181a and SIRT1 levels with severity and prognosis of neonatal acute respiratory distress syndrome

摘要:

目的 分析新生儿急性呼吸窘迫综合征（ARDS）血清microRNA-181a（miR-181a）、沉默信息调节因子2相关酶1（SIRT1）水平变化，探讨二者与其病情严重程度及预后的关系。方法 选取2017年10月—2021年7月东南大学附属中大医院江北院区收治的162例ARDS患儿为ARDS组，根据氧合指数分为轻度组60例、中度组53例、重度组49例；根据预后情况分为预后不良组68例和预后良好组94例。另选取同期64名健康新生儿为对照组。实时荧光定量聚合酶链反应（qRT-PCR）检测血清miR-181a mRNA相对表达量，酶联免疫吸附试验（ELISA）检测血清SIRT1、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平。Pearson/Spearman相关性分析ARDS患儿血清miR-181a、SIRT1水平与氧合指数、炎症因子的相关性。ROC曲线分析血清miR-181a、SIRT1水平单独及联合对ARDS患儿预后不良的评估价值。结果 ARDS组血清miR-181a mRNA相对表达量、IL-1β、IL-6、TNF-α水平均高于对照组（P <0.05）；SIRT1水平低于对照组（P <0.05）。重度组和中度组患儿血清miR-181a mRNA相对表达量、IL-1β、IL-6、TNF-α水平高于轻度组，且重度组血清miR-181a mRNA相对表达量、IL-1β、IL-6、TNF-α水平高于中度组（P <0.05）；而重度组和中度组患儿血清SIRT1水平低于轻度组，且重度组血清SIRT1水平低于中度组（P <0.05）。相关性分析显示，ARDS患儿血清miR-181a与SIRT1水平呈负相关（r_s =-0.788，P <0.05），与氧合指数、IL-1β、IL-6、TNF-α水平呈正相关（r =0.780、0.833、0.776和0.804，均P <0.05）；SIRT1与氧合指数、IL-1β、IL-6、TNF-α水平呈负相关（r_s/r =-0.836、-0.716、-0.691和-0.754，均P <0.05）。预后不良组血清miR-181a mRNA相对表达量高于预后良好组，SIRT1水平低于预后良好组（P <0.05）。ROC曲线结果显示，miR-181a评估ARDS患儿预后不良的最佳截断值为1.59，敏感性为80.88%（95% CI：0.717，0.857），特异性为70.21%（95% CI：0.652，0.757）；SIRT1评估ARDS患儿预后不良的最佳截断值为0.70 ng/ml，敏感性为76.47%（95% CI：0.712，0.796），特异性为87.23%（95% CI：0.832，0.917）。两者联合评估ARDS患儿预后不良的敏感性为85.29%（95% CI：0.788，0.902），特异性为81.91%（95% CI：0.774，0.886）。结论 新生儿ARDS血清miR-181a、SIRT1水平与ARDS患儿病情严重程度及预后密切相关，可作为新生儿ARDS预后评估指标。

Abstract:

Objective To analyze the changes of serum microRNA-181a (miR-181a) and silent information regulator factor 2-related enzyme 1 (SIRT1) levels in neonatal acute respiratory distress syndrome (ARDS), and to explore the relationship between them and the severity of their conditions and prognosis.Methods From October 2017 to July 2021, 162 children with ARDS admitted to our hospital were selected as the ARDS group, divided into mild (n = 60), moderate (n = 53) and severe (n = 49) groups according to oxygen index, and into poor prognosis (n = 68) and good prognosis (n = 94) groups according to prognosis. Another 64 healthy neonates were selected as the control group during the same period. Serum miR-181a levels were measured by qRT-PCR; serum SIRT1, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Pearson/Spearman correlation was used to analyze the correlation of serum miR-181a and SIRT1 levels with oxygen index and inflammatory factors in children with ARDS. ROC curves were used to analyze the value of serum miR-181a alone, SIRT1 levels alone, and the combination of the both for the assessment of poor prognosis in children with ARDS.Results The levels of serum miR-181a, IL-1β, IL-6, and TNF-α in the ARDS group were higher than those in the control group (P < 0.05); the level of SIRT1 was lower than that in the control group (P < 0.05). The levels of serum miR-181a, IL-1β, IL-6, and TNF-α in severe group and moderate group were higher than those in mild group, and serum miR-181a, IL-1β, IL-6, TNF-α in severe group were higher than that of the moderate group (P < 0.05); while the serum SIRT1 level in the severe group and the moderate group was lower than that of the mild group, the serum SIRT1 level of the severe group was lower than that of the moderate group (P < 0.05). Pearson / Spearman correlation analysis showed that there was a negative correlation between serum miR-181a and SIRT1 level in children with ARDS (r = -0.788, P < 0.05), and it was positively correlated with oxygen index, IL-1β, IL-6, and TNF-α levels (r = 0.780, 0.833, 0.776, 0.804, all P < 0.05); SIRT1 was negatively correlated with oxygen index, IL-1β, IL-6, and TNF-α levels (r_s/ r = -0.836, -0.716, -0.691, -0.754, all P < 0.05).The level of serum miR-181a in the poor prognosis group was higher than that in the good prognosis group (P < 0.05), and the level of SIRT1 was lower than that in the good prognosis group (P < 0.05). ROC curve showed that the best cut-off value of miR-181a in evaluating the poor prognosis of children with ARDS was 1.59, sensitivity was 80.88% (95% CI:0.717, 0.857), and specificity was 70.21% (95% CI：0.652, 0.757); the best cutoff value of SIRT1 for evaluating the poor prognosis of children with ARDS was 0.70 ng/ml, sensitivity was 76.47% (95% CI:0.712, 0.796), and specificity was 87.23% (95% CI: 0.832, 0.917). The sensitivity of miR-181a combined with SIRT1 for poor prognosis in children with ARDS the was 85.29% (95% CI: 0.788, 0.902), and the specificity was 81.91% (95% CI: 0.774, 0.886).Conclusion The up-regulation of serum miR-181a levels and down-regulation of SIRT1 levels in neonates with ARDS are closely related to the severity and prognosis of children with ARDS, and can be used as an indicator for assessing the prognosis of neonates with ARDS.