Abstract: Objective To explore the regulatory mechanism of recombinant human β defensin-2 (hBD2) and angiogenesis-related genes(ARGs) on angiogenesis in children with bronchopulmonary dysplasia (BPD), and to analyze their correlation with lung development markers. Methods A total of 56 children with BPD in Nanyang Central Hospital from January 2018 to November 2020 were selected as the observation group.And 56 children with healthy physical examination during the same period were selected as the control group according to the 1∶1 matching principle based on age and gender.The serum levels of hBD2 and ARGs[thrombin sensitive protein-1 (THBS-1) and transforming growth factor β1 (TGF-β1)] were compared between the two groups, as well as the levels of angiogenesis indexes [vascular endothelial growth factor (VEGF), Angiopoietin (Ang-1)] and lung development markers [kerbs von lungren 6 antigen (KL-6), serum Clara cell secretion protein (CC16)] in children with different serum hBD2 and ARGs levels.The relationship between serum hBD2, THBS-1, TGF-β1 and VEGF, Ang-1, KL-6, CC16 was analyzed, and the value of serum hBD2, ARGs in the diagnosis of BPD was evaluated. Results Serum hBD2 level in the observation group was significantly lower than that in the control group, and THBS-1 and TGF-β1 levels were significantly higher than those in the control group (t=6.888, 9.505, 9.065, P＜0.05).VEGF, Ang-1 and CC16 levels in children with low serum hBD2 level were significantly lower than those with high hBD2 level, and KL-6 level was higher than those with high hBD2 level (t=6.596, 4.389, 4.635, 4.248, P＜0.05).The serum levels of VEGF, Ang-1 and CC16 in children with low levels of THBS-1 and TGF-β1 were higher than those with high levels, and KL-6 level was lower than those with high levels of THBS-1 and TGF-β1 (THBS-1:t=5.671, 3.683, 4.193, 3.296, P＜0.05; TGF-β1: t=6.200, 3.721, 3.970, 3.808, P＜0.05).Serum hBD2 level was positively correlated with VEGF, Ang-1, CC16, and negatively correlated with KL-6.THBS-1 and TGF-β1 levels were negatively correlated with VEGF, Ang-1, CC16, and positively correlated with KL-6 (P＜0.05).The AUC of serum hBD2, THBS-1, and TGF-β1 alone in the diagnosis of BPD were 0.788, 0.857 and 0.805, respectively.And the AUC of the combined diagnosis of BPD was 0.931, with the sensitivity of 94.64% and the specificity of 87.50%. Conclusions hBD2 and ARGs are involved in the angiogenesis process of children with BPD and have a certain correlation with lung development markers.Monitoring hBD2 and ARGs can provide evidence for evaluating the angiogenesis and the degree of lung development in children with BPD, and help guide clinical protection measures to improve the prognosis of the disease.

Key words: bronchopulmonary dysplasia, recombinant human β defensin-2, angiogenesis-related genes, transforming growth factor β1, lung development marker, thrombin sensitive protein-1, angiogenesis index

摘要： 目的 探究支气管肺发育不良(BPD)患儿重组人β防御素-2(hBD2)、血管新生相关基因(ARGs)对血管生成的调控机制及与肺发育标志物相关性,以指导临床采取相应干预措施,改善疾病预后。方法 选取南阳市中心医院2018年1月-2020年11月BPD患儿56例作为观察组,另根据年龄、性别按照1∶1匹配原则选取同期健康体检小儿56例作为对照组。比较两组血清hBD2、ARGs[凝血酶敏感蛋白-1(THBS-1)、转化生长因子β1(TGF-β1)]水平,不同血清hBD2、ARGs水平患儿血管生成指标[血管内皮生长因子(VEGF)、血管生成素(Ang-1)]水平、肺发育标志物[Ⅱ型肺泡细胞表面抗原6(KL-6)、血清Clara细胞分泌蛋白(CC16)]水平,分析血清hBD2、THBS-1、TGF-β1与VEGF、Ang-1、KL-6、CC16的关系,并评价血清hBD2、ARGs对BPD诊断价值。结果 观察组血清hBD2低于对照组,THBS-1、TGF-β1高于对照组(t=6.888、9.505、9.065,P＜0.05);血清hBD2低水平患儿VEGF、Ang-1、CC16低于高水平患儿,KL-6高于高水平患儿(t=6.596、4.389、4.635、4.248,P＜0.05);血清THBS-1、TGF-β低水平患儿VEGF、Ang-1、CC16高于高水平患儿,KL-6低于高水平患儿(THBS-1:t=5.671、3.683、4.193、3.296,P＜0.05;TGF-β:t=6.200、3.721、3.970、3.808,P＜0.05);血清hBD2与VEGF、Ang-1、CC16呈正相关,与KL-6呈负相关,THBS-1、TGF-β1分别与VEGF、Ang-1、CC16呈负相关,与KL-6呈正相关(P＜0.05);血清hBD2、THBS-1、TGF-β1单独诊断BPD的AUC依次为0.788、0.857、0.805,联合诊断BPD的AUC为0.931,敏感度为94.64%,特异度为87.50%。结论 hBD2、ARGs参与BPD患儿血管生成过程,与肺发育标志物具有一定相关性,监测hBD2、ARGs基因可对BPD患儿血管生成、肺发育程度提供评估依据,。

关键词: 支气管肺发育不良, 重组人β防御素-2, 血管新生相关基因, 转化生长因子β1, 肺发育标志物, 凝血酶敏感蛋白-1, 血管生成指标