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。
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.