早产儿支气管肺发育不良的代谢组学改变

吴彦彦, 卜琪琪, 王馨, 李涛, 吴红燕, 康乐, 王颍源, 刘大鹏, 郭静, 王彩君, 康文清

中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (12) : 1475-1481.

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中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (12) : 1475-1481. DOI: 10.7499/j.issn.1008-8830.2505102
论著·临床研究

早产儿支气管肺发育不良的代谢组学改变

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Metabolomic alterations in preterm infants with bronchopulmonary dysplasia

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摘要

目的 分析支气管肺发育不良(bronchopulmonary dysplasia, BPD)患儿在校正胎龄(postmenstrual age, PMA)36周的血清代谢组学改变,筛选其潜在生物标志物及相关代谢通路,并分析其与患儿近期呼吸结局的关系。 方法 采用回顾性病例对照研究,纳入2024年1—12月间郑州大学附属儿童医院收治的胎龄28~32周20例BPD患儿,以及20例胎龄、体重、性别匹配的非BPD早产儿,于PMA 36周进行血清非靶向代谢组学分析。 结果 共筛选出13种可区分BPD的潜在生物标志物(曲线下面积>0.75,P<0.05),其中对苯二甲酸、磷脂酰肌醇、富马酸及溶血磷脂酸等8种显著上调(差异倍数≥1.5);7α-羟基-3-氧代-4-胆甾烯酸酯、磷脂酰胆碱等5种显著下调(差异倍数≤1/1.5)。通路分析显示,甘油磷脂代谢、苯丙氨酸代谢等5条通路与BPD发生相关。甘油磷脂代谢与胆汁酸代谢紊乱可能影响BPD患儿近期不良呼吸结局。 结论 该研究筛选出的13种显著差异代谢物有望成为诊断BPD的标志物;甘油磷脂代谢与BPD的发生和近期呼吸不良结局相关。

Abstract

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia (BPD) at postmenstrual age (PMA) 36 weeks, screen potential biomarkers and associated metabolic pathways, and assess their relationship with short-term respiratory outcomes. Methods A retrospective case-control study was conducted. Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included. Twenty infants with BPD and 20 gestational age-, birth weight-, and sex-matched non-BPD preterm infants were included. Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis, and associations with short-term respiratory outcomes were analyzed. Results Thirteen potential biomarkers distinguishing BPD were identified (area under the curve >0.75, P<0.05). Eight biomarkers—including terephthalic acid, phosphatidylinositol, fumarate, and lysophosphatidic acid—were significantly upregulated (FC≥1.5), while five biomarkers, such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine, were significantly downregulated (FC≤1/1.5). Pathway analysis indicated five pathways associated with BPD, including glycerophospholipid metabolism and phenylalanine metabolism. Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD. Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD. Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

关键词

支气管肺发育不良 / 非靶向代谢组学 / 血清 / 显著差异代谢物 / 早产儿

Key words

Bronchopulmonary dysplasia / Untargeted metabolomics / Serum / Differential metabolite / Preterm infant

引用本文

导出引用
吴彦彦, 卜琪琪, 王馨, . 早产儿支气管肺发育不良的代谢组学改变[J]. 中国当代儿科杂志. 2025, 27(12): 1475-1481 https://doi.org/10.7499/j.issn.1008-8830.2505102
Yan-Yan WU, Qi-Qi BU, Xin WANG, et al. Metabolomic alterations in preterm infants with bronchopulmonary dysplasia[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(12): 1475-1481 https://doi.org/10.7499/j.issn.1008-8830.2505102

参考文献

[1]
Lui K, Lee SK, Kusuda S, et al. Trends in outcomes for neonates born very preterm and very low birth weight in 11 high-income countries[J]. J Pediatr, 2019, 215: 32-40.e14. DOI: 10.1016/j.jpeds.2019.08.020 .
[2]
蒋思远, 杨传忠, 田秀英, 等. 中国新生儿协作网出生胎龄22~25周超早产儿出院预后及治疗现状[J]. 中华儿科杂志, 2024, 62(1): 22-28. DOI: 10.3760/cma.j.cn112140-20231017-00296 .
[3]
Davidson LM, Berkelhamer SK. Bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary outcomes[J]. J Clin Med, 2017, 6(1): 4. PMCID: PMC5294957. DOI: 10.3390/jcm6010004 .
[4]
宋媛媛, 祁增华, 蔡宗苇. 多组学质谱分析技术在化学暴露组研究中的应用[J]. 色谱, 2024, 42(2): 120-130. PMCID: PMC10877483. DOI: 10.3724/SP.J.1123.2023.10001 .
[5]
肖吉英, 何静, 黄淑敏, 等. 代谢组学在儿童支气管哮喘中的应用研究进展[J]. 中华儿科杂志, 2022, 60(9): 960-963. DOI: 10.3760/cma.j.cn112140-20220613-00546 .
[6]
黄锐, 纪翔, 熊丹. 代谢组学技术在恶性肿瘤诊疗研究中的进展及应用[J]. 临床检验杂志, 2023, 41(11): 854-857. DOI: 10.13602/j.cnki.jcls.2023.11.11 .
[7]
Baraldi E, Giordano G, Stocchero M, et al. Untargeted metabolomic analysis of amniotic fluid in the prediction of preterm delivery and bronchopulmonary dysplasia[J]. PLoS One, 2016, 11(10): e0164211. PMCID: PMC5068788. DOI: 10.1371/journal.pone.0164211 .
[8]
Rüdiger M, von Baehr A, Haupt R, et al. Preterm infants with high polyunsaturated fatty acid and plasmalogen content in tracheal aspirates develop bronchopulmonary dysplasia less often[J]. Crit Care Med, 2000, 28(5): 1572-1577. DOI: 10.1097/00003246-200005000-00052 .
[9]
You Y, Wang L, Liu C, et al. Early metabolic markers as predictors of respiratory complications in preterm infants with bronchopulmonary dysplasia[J]. Early Hum Dev, 2024, 190: 105950. DOI: 10.1016/j.earlhumdev.2024.105950 .
[10]
刘颖, 张双船. 代谢组学筛选支气管肺发育不良新的生物标志物研究进展[J]. 国际儿科学杂志, 2021, 48(3): 178-181. DOI: 10.3760/cma.j.issn.1673-4408.2021.03.008 .
[11]
Higgins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary dysplasia: executive summary of a workshop[J]. J Pediatr, 2018, 197: 300-308. PMCID: PMC5970962. DOI: 10.1016/j.jpeds.2018.01.043 .
[12]
邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 5版. 北京: 人民卫生出版社, 2019.
[13]
Zhou X, Zhang J, Hu F, et al. Non-targeted metabolomics reveals the effects of fermented methods on the flavor, quality, and metabolites of whipping cream[J]. Food Chem X, 2025, 27: 102376. DOI: 10.1016/j.fochx.2025.102376 .
[14]
Xu Y, Wang X, Han D, et al. Revealing the mechanism of Jiegeng decoction attenuates bleomycin-induced pulmonary fibrosis via PI3K/Akt signaling pathway based on lipidomics and transcriptomics[J]. Phytomedicine, 2022, 102: 154207. DOI: 10.1016/j.phymed.2022.154207 .
[15]
Akella A, Deshpande SB. Pulmonary surfactants and their role in pathophysiology of lung disorders[J]. Indian J Exp Biol, 2013, 51(1): 5-22.
[16]
Cetinkaya M, Cansev M, Kafa IM, et al. Cytidine 5'-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model[J]. Pediatr Res, 2013, 74(1): 26-33. DOI: 10.1038/pr.2013.68 .
[17]
Oikonomou N, Mouratis MA, Tzouvelekis A, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2012, 47(5): 566-574. DOI: 10.1165/rcmb.2012-0004OC .
[18]
Kim SJ, Howe C, Mitchell J, et al. Autotaxin loss accelerates intestinal inflammation by suppressing TLR4-mediated immune responses[J]. EMBO Rep, 2020, 21(10): e49332. PMCID: PMC7534615. DOI: 10.15252/embr.201949332 .
[19]
王芳, 陈曦. 溶血磷脂酸信号在心血管疾病中的作用及潜在临床应用价值[J]. 中华心血管病杂志, 2023, 51(7): 782-789. DOI: 10.3760/cma.j.cn112148-20230519-00287 .
[20]
Ntatsoulis K, Karampitsakos T, Tsitoura E, et al. Commonalities between ARDS, pulmonary fibrosis and COVID-19: the potential of autotaxin as a therapeutic target[J]. Front Immunol, 2021, 12: 687397. PMCID: PMC8522582. DOI: 10.3389/fimmu.2021.687397 .
[21]
Ishihara Y, Kajino M, Iwamoto Y, et al. Impact of artificial sunlight aging on the respiratory effects of polyethylene terephthalate microplastics through degradation-mediated terephthalic acid release in male mice[J]. Toxicol Sci, 2025, 203(2): 242-252. DOI: 10.1093/toxsci/kfae135 .
[22]
Zecchini V, Paupe V, Herranz-Montoya I, et al. Fumarate induces vesicular release of mtDNA to drive innate immunity[J]. Nature, 2023, 615(7952): 499-506. PMCID: PMC10017517. DOI: 10.1038/s41586-023-05770-w .
[23]
Ma Y, Zhang Y, Li R, et al. Mechanism of taurine reducing inflammation and organ injury in sepsis mice[J]. Cell Immunol, 2022, 375: 104503. DOI: 10.1016/j.cellimm.2022.104503 .
[24]
Ma Y, Wang Y, Xie A, et al. Activation of LXR signaling ameliorates apoptosis of alveolar epithelial cells in bronchopulmonary dysplasia[J]. Respir Res, 2024, 25(1): 399. PMCID: PMC11545640. DOI: 10.1186/s12931-024-03031-6 .

脚注

所有作者均声明无利益冲突。

致谢

感谢首都医科大学附属北京儿童医院新生儿中心黑明燕教授对论文修改的指导。

基金

河南省科技发展计划(242102311028)

编委: 王颖

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