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,。
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.
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
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
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参考文献
[1] Thébaud B,Goss KN,Laughon M,et al.Bronchopulmonary dysplasia[J].Nat Rev Dis Primers,2019,5(1):78.
[2] 伊丽丽.早产儿支气管肺发育不良的发病机制及治疗现状[J].国际儿科学杂志,2018,45(3):212-215.
[3] Tracy MK,Berkelhamer SK.Bronchopulmonary dysplasia and pulmonary outcomes of prematurity[J].Pediatr Ann,2019,48(4):148-153.
[4] Hwang JS,Rehan VK.Recent advances in bronchopulmonary dysplasia:Pathophysiology,prevention,and treatment[J].Lung,2018,196(2):129-138.
[5] 章礼真.支气管肺发育不良发病机制及防治策略研究进展[J].安徽医学,2017,38(3):385-388.
[6] 沈桢巍,雷撼,李鹏.人β防御素2抗氧化型低密度脂蛋白诱导的单核细胞泡沫化的作用机制研究[J].中华传染病杂志,2019,37(5):287-291.
[7] Pinkerton JW,Kim RY,Koeninger L,et al.Human β-defensin-2 suppresses key features of asthma in murine models of allergic airways disease[J].Clin Exp Allergy,2021,51(1):120-131.
[8] 杨娇娇,陈翠娥,孙媛媛,等.重组人β防御素-2基因对支气管肺发育不良新生鼠肺泡及肺血管发育的影响[J].浙江医学,2019,41(22):2389-2393,2407,前插4.
[9] 杨敏,黄建宝,孟燕妮,等.血管新生相关基因与早产儿支气管肺发育不良的相关性研究[J].中国妇幼保健,2018,33(17):3936-3939.
[10] 左敬叶,王艺睿,杨宇婷.早产儿支气管肺发育不良的发病机制研究进展[J].国际儿科学杂志,2019,46(11):831-834.
[11] 潘建光,张雷,文文,等.肺爆震伤大鼠早期血管内皮生长因子、神经菌毛素-1的变化及其与肺损伤程度的相关性[J].解放军医学杂志,2019,44(1):63-69.
[12] Ahn SY,Park WS,Kim YE,et al.Vascular endothelial growth factor mediates the therapeutic efficacy of mesenchymal stem cell-derived extracellular vesicles against neonatal hyperoxic lung injury[J].Exp Mol Med,2018,50(4):1-12.
[13] 陈鑫,许惠芬,王林华,等.血管生成素及其受体与降钙素原联合检测在急性肺损伤诊治中的作用[J].安徽医药,2019,23(2):320-323.
[14] 王晓容,蒋海清,赵苏.Ang-1与Ang-2在毛细支气管炎患儿血清和诱导痰上清液中的表达及临床意义[J].华南国防医学杂志,2020,34(3):185-188.
[15] 廖玲洁.支气管肺发育不良的炎性机制及抗趋化干预[D].武汉:华中科技大学,2004.
[16] 张明霞,赵瑞卿,李庆霞,等.早产儿支气管肺发育不良的影响因素分析[J].蚌埠医学院学报,2017,42(10):1321-1323.
[17] 李科果,富建华.支气管肺发育不良早产儿肺功能的研究进展[J].国际儿科学杂志,2020,47(6):403-406.
[18] 李兴朝,李涛,谢集建,等.枸橼酸咖啡因联合肺泡表面活性物质治疗新生儿呼吸窘迫综合征的疗效及对血清BMP-7、CC16、SF水平的影响[J].现代生物医学进展,2019,19(15):2953-2956,2965.
[19] Almuntashiri S,Zhu Y,Han Y,et al.Club cell secreted protein CC16:Potential applications in prognosis and therapy for pulmonary diseases[J].J Clin Med,2020,9(12):4039.
[20] 王冉冉,田美伊,杨金水,等.血清KL-6水平对评价结缔组织病间质性肺疾病作用的研究[J].中国临床医生杂志,2017,45(3):36-40.
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