极低体重儿氧暴露后血清外泌体miR-30a、miR-34a变化与支气管肺发育不良的相关性-东南大学学报医学版

极低体重儿氧暴露后血清外泌体miR-30a、miR-34a变化与支气管肺发育不良的相关性

单位：1. 衡水市妇幼保健院检验科, 河北衡水 053000;
2. 衡水市人民医院检验科, 河北衡水 053000

分类号：R722.6

出版年·卷·期（页码）：2021·40·第三期（298-305）

摘要：

目的：探讨极低体重早产儿氧暴露后血清外泌体miR-30a、miR-34a变化趋势以及其与支气管肺发育不良（BPD）的关系。方法：选取2018年1月至2020年1月在衡水市妇幼保健院新生儿重症监护室住院>28 d的极低体重早产儿，包括56例BPD患儿（BPD组）和50例非BPD早产儿（非BPD组）。采集产后1、7、14、21、28 d新生儿循环血，分离血清外泌体，并采用实时荧光定量PCR法检测外泌体miR-30a、miR-34a水平。结果：产后14、21、28 d时BPD组外泌体miR-30a水平低于非BPD组，同时外泌体miR-34a水平高于非BPD组（P<0.05）。产后21、28 d时中重度BPD亚组外泌体miR-30a水平低于轻度BPD组，并且男性早产儿降低更明显（P<0.05）；同时中重度BPD亚组外泌体miR-34a水平高于轻度BPD亚组（P<0.05），但是男性和女性相比差异无统计学意义（P>0.05）。绘制ROC曲线，产后28 d血清外泌体miR-30a、miR-34a诊断BPD的曲线下面积分别为0.868（95%CI：0.795~0.915）和0.798（95%CI：0.703~0.854）。结论：随着氧暴露时间的延长，极低体重BPD早产儿血清外泌体miR-30a水平逐渐降低，尤其是男性BPD患儿降低更明显，同时外泌体miR-34a水平逐渐升高。检测血清外泌体miR-30a、miR-34a表达有助于BPD诊断以及对病情进展的评估。

Objective: To investigate the relationship between the changes of serum exosomal miR-30a, miR-34a and bronchopulmonary dysplasia (BPD) in very low birth weight(VLBW) preterm infants during oxygen exposure. Methods: From January 2018 to January 2020, the preterm infants with VLBW hospitalized in Neonatal Intensive Care Unit of Hengshui Maternal and Child Health Care Hospital for more than 28 days were selected, including 56 cases of BPD(BPD group) and 50 cases of non BPD(non BPD group) preterm infants. Neonatal circulating blood at 1, 7, 14, 21 and 28 days after delivery were collected. Serum exosomes were isolated, and the levels of exosomal miR-30a and miR-34a were detected by real-time quantitative PCR. Results: At the 14th, 21th and 28th day after delivery, the levels of exosomal miR-30a of BPD group were lower than those of non BPD group, and the levels of exosomal miR-34a of BPD group were higher than those of non BPD group(P<0.05). At the 21th and 28th day after delivery, the level of exosomal miR-30a in the moderate & severe BPD subgroup was lower than that in the mild BPD group, while the male preterm infants decreased more significantly (P<0.05); meanwhile, the level of exosomal miR-34a in the moderate & severe BPD subgroup was higher than that of the mild BPD subgroup(P<0.05), but there was no significant difference between male and female(P>0.05). ROC curve showed that the area under the curve of exosomal miR-30a and miR-34a at the 28th day after delivery for the diagnosis of BPD were 0.868(95% CI: 0.795-0.915) and 0.798(95% CI: 0.703-0.854) respectively. Conclusion: With the prolongation of oxygen exposure time, the level of serum exosomal miR-30a in VLBW BPD preterm infants decreased gradually, especially in male BPD children, while the level of exosomal miR-34a increased gradually. Serum exosomal miR-30a and miR-34a would be helpful to the diagnosis of BPD and the evaluation of disease progression.

参考文献：

[1] 林慈丽, 盛苗苗, 卢赛丹, 等. 早产儿支气管肺发育不良危险因素研究[J]. 中国预防医学杂志, 2018, 19(12):928-932.
[2] 徐凤丹, 王优, 吴文燊, 等. 高氧暴露对新生小鼠肺部炎性反应及纤维化的影响[J]. 中国医药导报, 2017, 14(26):21-24, 181.
[3] ZHANG Y, DONG X, LINGAPPAN K.Role of hif-1α-mir30a-snai1 axis in neonatal hyperoxic lung injury[J]. Oxid Med Cell Longev, 2019, 1155(10):1-9.
[4] MIZUNO S, BOGAARD H J, GOMEZ-ARROYO J, et al. MicroRNA-199a-5p is associated with hypoxia-inducible factor-1alpha expression in lungs from patients with COPD[J]. Chest, 2012, 142(3):663-672.
[5] LAL C V, OLAVE N, TRAVERS C, et al. Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants[J]. JCI Insight, 2018, 3(5):e93994.
[6] 邵肖梅, 叶鸿瑁, 丘小汕.实用新生儿学[M]. 4版.北京:人民卫生出版社, 2011:340-347.
[7] 杨蛟, 努尔亚·热加甫, 刘永巧.2015—2018年早产儿支气管肺发育不良的发病情况和相关因素分析[J]. 中国儿童保健杂志, 2019, 27(10):1102-1104, 1132.
[8] DAS P, SYED M A, SHAH D, et al. miR34a:a master regulator in the pathogenesis of bronchopulmonary dysplasia[J]. Cell Stress, 2018, 2(2):34-36.
[9] SYED M, DAS P, PAWAR A, et al. Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs[J]. Nat Commun, 2017, 8(1):1173.
[10] O'CONNOR M G, MOORE P E.Sex differences after NICU discharge in infants with BPD:observations from one center[J]. Pediatr Pulmonol, 2017, 52(1):7-9.
[11] ZHANG Y, COARFA C, DONG X, et al. MicroRNA-30a as a candidate underlying sex-specific differences in neonatal hyperoxic lung injury:implications for BPD[J]. Am J Physiol Lung Cell Mol Physiol, 2019, 316(1):L144-L156.
[12] 张华伟, 于丽佳, 张春民, 等. 外泌体miRNA的生物学功能及其在肺纤维化疾病中的调控作用[J]. 生物化学与生物物理进展, 2019, 43(11):1073-1084.
[13] WILLIS G R, FERNANDEZ-GONZALEZ A, ANASTAS J, et al. Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation[J]. Am J Respir Crit Care Med, 2018, 197(1):104-116.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录