支气管肺发育不良早产儿血清miR-15b和血管内皮生长因子动态变化及其在神经系统发育评估中的价值

陈前, 张沛佩, 芦庆花, 万振霞, 黄磊

中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (9) : 1062-1070.

PDF(697 KB)
HTML
PDF(697 KB)
HTML
中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (9) : 1062-1070. DOI: 10.7499/j.issn.1008-8830.2412039
论著·临床研究

支气管肺发育不良早产儿血清miR-15b和血管内皮生长因子动态变化及其在神经系统发育评估中的价值

作者信息 +

Dynamic changes in serum microRNA-15b and vascular endothelial growth factor in preterm infants with bronchopulmonary dysplasia and their value in assessing neurodevelopment

Author information +
文章历史 +

摘要

目的 探讨轻度和中重度支气管肺发育不良(bronchopulmonary dysplasia, BPD)早产儿血清微小核糖核酸(microRNAs, miR)-15b、血管内皮生长因子(vascular endothelial growth factor, VEGF)动态变化及其在近期神经系统发育评估中的价值。 方法 回顾性分析2020年1月—2023年2月入住新生儿重症监护室的156例BPD早产儿的临床资料。依据BPD分度分为轻度组(88例)与中重度组(68例)。于出生后第1、7、14、28天检测血清中miR-15b和VEGF水平。使用重复测量方差分析评估血清miR-15b、VEGF水平的动态变化。使用逐步回归法和Bootstrap法检验分析VEGF在miR-15b和近期神经系统发育之间的中介效应。使用logistic回归分析影响神经发育不良的因素。 结果 轻度组血清miR-15b水平随时间呈明显降低趋势,VEGF呈明显上升趋势(P<0.05);中重度组血清miR-15b水平随时间呈上升趋势,VEGF水平呈下降趋势(P<0.05)。血清miR-15b、VEGF水平是神经发育评估结果的重要影响因素,存在独立相关性(P<0.001)。中介效应分析显示,miR-15b通过抑制VEGF表达间接影响近期神经系统发育[间接效应值=-0.705(95%CI:-1.178~-0.372)],该间接效应占总效应的54.36%。 结论 轻度与中重度BPD早产儿血清miR-15b、VEGF变化趋势不同;miR-15b主要通过VEGF影响神经系统发育。

Abstract

Objective To investigate the dynamic changes in serum microRNA-15b (miR-15b) and vascular endothelial growth factor (VEGF) in preterm infants with mild or moderate-to-severe bronchopulmonary dysplasia (BPD), as well as their value in assessing short-term neurodevelopment. Methods A retrospective analysis was conducted on the medical data of 156 preterm infants with BPD who were admitted to the neonatal intensive care unit from January 2020 to February 2023. According to the severity of BPD, they were divided into a mild group (n=88) and a moderate-to-severe group (n=68). Serum levels of miR-15b and VEGF were measured on postnatal days 1, 7, 14, and 28. Repeated measures analysis of variance was used to assess the dynamic changes in serum levels of miR-15b and VEGF. The mediating effect of VEGF between miR-15b and short-term neurological development was tested and analyzed using the stepwise regression method and the Bootstrap method. Logistic regression analysis was used to identify factors influencing adverse neurodevelopmental outcomes. Results In the mild group, there was a significant reduction in the serum level of miR-15b and a significant increase in VEGF over time (P<0.05), while in the moderate-to-severe group, there was a significant increase in miR-15b and a significant reduction in VEGF over time (P<0.05). Serum miR-15b and VEGF levels were important factors influencing neurodevelopmental outcomes, showing independent correlations (P<0.001). The mediating effect analysis indicated that miR-15b indirectly affected short-term neurodevelopment by inhibiting VEGF expression [indirect effect: -0.705 (95%CI: -1.178 to -0.372)], with the indirect effect accounting for 54.36% of the total effect. Conclusions There are different changing trends in serum levels of miR-15b and VEGF in preterm infants with mild and moderate-to-severe BPD. miR-15b primarily influences neurodevelopment through VEGF.

关键词

支气管肺发育不良 / 神经发育 / miR-15b / 血管内皮生长因子 / 早产儿

Key words

Bronchopulmonary dysplasia / Neurodevelopment / microRNA-15b / Vascular endothelial growth factor / Preterm infant

引用本文

导出引用
陈前, 张沛佩, 芦庆花, . 支气管肺发育不良早产儿血清miR-15b和血管内皮生长因子动态变化及其在神经系统发育评估中的价值[J]. 中国当代儿科杂志. 2025, 27(9): 1062-1070 https://doi.org/10.7499/j.issn.1008-8830.2412039
Qian CHEN, Pei-Pei ZHANG, Qing-Hua LU, et al. Dynamic changes in serum microRNA-15b and vascular endothelial growth factor in preterm infants with bronchopulmonary dysplasia and their value in assessing neurodevelopment[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(9): 1062-1070 https://doi.org/10.7499/j.issn.1008-8830.2412039

参考文献

[1]
Gibbs K, Jensen EA, Alexiou S, et al. Ventilation strategies in severe bronchopulmonary dysplasia[J]. Neoreviews, 2020, 21(4): e226-e237. DOI: 10.1542/neo.21-4-e226 .
[2]
Gan S, Mao J, Pan Y, et al. hsa-miR-15b-5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis[J]. Exp Ther Med, 2021, 22(5): 1208. PMCID: PMC8422401. DOI: 10.3892/etm.2021.10642 .
[3]
Zhu Y, Hou H, Li Y, et al. Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeII epithelial cell[J]. Redox Rep, 2024, 29(1): 2387465. PMCID: PMC11302460. DOI: 10.1080/13510002.2024.2387465 .
[4]
Mariduena J, Ramagopal M, Hiatt M, et al. Vascular endothelial growth factor levels and bronchopulmonary dysplasia in preterm infants[J]. J Matern Fetal Neonatal Med, 2022, 35(8): 1517-1522. DOI: 10.1080/14767058.2020.1760826 .
[5]
Zhang L, Wang P, Shen Y, et al. Mechanism of lncRNA H19 in regulating pulmonary injury in hyperoxia-induced bronchopulmonary dysplasia newborn mice[J]. Am J Perinatol, 2022, 39(10): 1089-1096. DOI: 10.1055/s-0040-1721498 .
[6]
Miller AN, Shepherd EG, El-Ferzli G, et al. Multidisciplinary bronchopulmonary dysplasia care[J]. Expert Rev Respir Med, 2023, 17(11): 989-1002. DOI: 10.1080/17476348.2023.2283120 .
[7]
Stieren ES, Sankaran D, Lakshminrusimha S, et al. Comorbidities and late outcomes in neonatal pulmonary hypertension[J]. Clin Perinatol, 2024, 51(1): 271-289. PMCID: PMC10850767. DOI: 10.1016/j.clp.2023.10.002 .
[8]
Jensen EA, Watterberg KL. Postnatal corticosteroids to prevent bronchopulmonary dysplasia[J]. Neoreviews, 2023, 24(11): e691-e703. DOI: 10.1542/neo.24-11-e691 .
[9]
Xing Y, Fu J, Yang H, et al. MicroRNA expression profiles and target prediction in neonatal Wistar rat lungs during the development of bronchopulmonary dysplasia[J]. Int J Mol Med, 2015, 36(5): 1253-1263. PMCID: PMC4601749. DOI: 10.3892/ijmm.2015.2347 .
[10]
Sahni M, Bhandari V. Patho-mechanisms of the origins of bronchopulmonary dysplasia[J]. Mol Cell Pediatr, 2021, 8(1): 21. PMCID: PMC8665964. DOI: 10.1186/s40348-021-00129-5 .
[11]
Gentle SJ, Travers CP, Clark M, et al. Patent ductus arteriosus and development of bronchopulmonary dysplasia-associated pulmonary hypertension[J]. Am J Respir Crit Care Med, 2023, 207(7): 921-928. PMCID: PMC10111998. DOI: 10.1164/rccm.202203-0570OC .
[12]
Bai Y, Gong X, Dong R, et al. Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p[J]. Genes Dis, 2022, 9(2): 456-465. PMCID: PMC8843884. DOI: 10.1016/j.gendis.2020.07.013 .
[13]
Wang F, Zhang M. Circ_001209 aggravates diabetic retinal vascular dysfunction through regulating miR-15b-5p/COL12A1[J]. J Transl Med, 2021, 19(1): 294. PMCID: PMC8265106. DOI: 10.1186/s12967-021-02949-5 .
[14]
Zhao T, Jin Q, Kong L, et al. microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis[J]. J Bioenerg Biomembr, 2022, 54(1): 17-30. DOI: 10.1007/s10863-021-09919-y .
[15]
Perrone S, Manti S, Buttarelli L, et al. Vascular endothelial growth factor as molecular target for bronchopulmonary dysplasia prevention in very low birth weight infants[J]. Int J Mol Sci, 2023, 24(3): 2729. PMCID: PMC9916882. DOI: 10.3390/ijms24032729 .
[16]
Bhagavatheeswaran S, Ramachandran V, Shanmugam S, et al. Isopimpinellin extends antiangiogenic effect through overexpression of miR-15b-5p and downregulating angiogenic stimulators[J]. Mol Biol Rep, 2022, 49(1): 279-291. DOI: 10.1007/s11033-021-06870-4 .
[17]
Yang Y, Liu Y, Li Y, et al. MicroRNA-15b targets VEGF and inhibits angiogenesis in proliferative diabetic retinopathy[J]. J Clin Endocrinol Metab, 2020, 105(11): 3404-3415. PMCID: PMC7947967. DOI: 10.1210/clinem/dgaa538 .

脚注

所有作者均声明无利益冲突。

基金

山东省医药卫生科技发展计划项目(202406011275)

编委: 张辉

版权

版权所有 © 2023中国当代儿科杂志
PDF(697 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/