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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (03) : 342 -346. doi: 10.3877/cma.j.issn.1673-5250.2015.03.012

所属专题： 文献；

论著

支气管肺发育不良早产儿肝细胞生长因子、血管内皮生长因子水平变化及其相关性
高原1, 刘花兰2, 包云光1, 赵婵1, 余波3, 林振浪3,*,*()   
  1. 1. 321000　浙江省金华市中心医院儿科
    2. 325027　浙江省温州医科大学附属二院育英儿童医院新生儿科；315012　浙江省宁波妇女儿童医院儿科
    3. 325027　浙江省温州医科大学附属二院育英儿童医院新生儿科
  • 收稿日期:2014-12-15 修回日期:2015-04-28 出版日期:2015-06-01
  • 通信作者: 林振浪

Dynamic levels of hepatocyte growth factor and vascular endothelial growth factor in the development of bronchopulmonary dysplasia

Yuan Gao1, Hualan Liu2, Yunguang Bao1, Chan Zhao1, Bo Yu3, Zhenlang Lin3()   

  1. 1. Department of Pediatrics, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
    2. 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China; Ningbo Women & Children's Hospital, Ningbo 315012, Zhejiang Province, China
    3. 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
  • Received:2014-12-15 Revised:2015-04-28 Published:2015-06-01
  • Corresponding author: Zhenlang Lin
  • About author:
    Corresponding author: Lin Zhenlang, Email:
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高原, 刘花兰, 包云光, 赵婵, 余波, 林振浪. 支气管肺发育不良早产儿肝细胞生长因子、血管内皮生长因子水平变化及其相关性[J/OL]. 中华妇幼临床医学杂志(电子版), 2015, 11(03): 342-346.

Yuan Gao, Hualan Liu, Yunguang Bao, Chan Zhao, Bo Yu, Zhenlang Lin. Dynamic levels of hepatocyte growth factor and vascular endothelial growth factor in the development of bronchopulmonary dysplasia[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(03): 342-346.

目的

探讨发生支气管肺发育不良(BPD)的早产儿支气管肺泡灌洗液(BALF)中肝细胞生长因子(HGF)和血管内皮生长因子(VEGF)表达水平变化及其相关性。

方法

选择2009年10月至2013年6月浙江省金华市中心医院(浙江大学金华医院)和温州医科大学附属二院育英儿童医院收治的生后24 h内行气管插管呼吸机辅助治疗的60例早产儿为研究对象。根据早产儿是否为BPD，将其分为BPD组(n＝22)和非BPD组(n＝38)。两组患儿的胎龄、出生体质量、性别构成比、生后5 min Apagar评分、肺表面活性物质(PS)应用次数等一般临床资料比较，差异无统计学意义(P>0.05)。两组患儿均于在气管插管拔除之前采集BALF，采集时间点分别在生后第1，3，7，14天。采用酶联免疫吸附测定(ELISA)法测定BALF上清液中HGF、VEGF及sIgA水平，并对两组进行对比分析。本研究遵循的程序符合金华市中心医院(浙江大学金华医院)和温州医科大学附属二院育英儿童医院人体试验委员会制定的伦理学标准，得到该委员会批准，征得受试对象监护人的知情同意，并与之签署临床研究知情同意书。

结果

①BPD组患儿接受呼吸机治疗时间明显较非BPD组长(Z＝3.283，P＝0.001)。②早产儿生后2周内不同时间点，BPD组患儿BALF中HGF及VEGF水平均低于非BPD组(P<0.05)，且随着日龄的增加，BPD组的HGF水平逐渐下降，而VEGF水平逐渐升高。③出生后第3天HGF及VEGF水平与BPD转归呈负相关关系(OR＝0.806，95%CI：0.764～0.851，P<0.01；OR＝0.288，95%CI：0.189～0.439，P<0.01)。

结论

BPD早产儿BALF中HGF、VEGF水平明显低于非BPD早产儿。出生后第3天的HGF、VEGF低水平表达与BPD发生具有相关性。

关键词: 支气管肺发育不良, 肝细胞生长因子, 血管内皮生长因子, 婴儿，早产
Objective

To investigate the dynamic levels of hepatocyte growth factor (HGF), vascular endothelial growth factor(VEGF) in bronchopulmonary dysplasia (BPD), so that to reveal the relationship between two growth factors and BPD.

Methods

Sixty preterm newborns (<32 weeks' gestation) who visited the department of Pediatrics, Jinhua Central Hospital and The 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University from October 2009 to June 2013 were included in this study. All of them were received mechanical ventilation within 24 h after birth. They were divided into BPD group (n=22) and BPD-free group (n=38) according to the diagnostic criteria of BPD. There were no significant differences between two groups in the aspects of gestational weeks, birth weight, constituent ratio of gender, 5 min Apgar scores and application numbers of pulmonary surfactant (PS), and so on (P>0.05). Bronchoalveolar lavage fluid(BALF) samples were collected from 60 ventilated preterm infants on 1st, 3rd, 7th, 14th day after birth. The levels of HGF, VEGF and secreted immunoglobulin (sIg) A were quantified by enzyme linked immunosorbent assay (ELISA), at the same time, clinical information were collected. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Jinhua Central Hospital and The 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University. Informed consent was obtained from the parents of each participating child.

Results

①Ventilator therapy duration in BPD group was significantly longer than that in BPD-free group (Z=3.283, P=0.001). ②BPD group has lower levels of VEGF and HGF than those in BPD-free group at four different time-points (P<0.05), while the levels of VEGF became higher and higher, and the levels of HGF became lower and lower. The levels of HGF and VEGF on the 3rd day after birth showed negative connection with BPD(OR=0.806, 95%CI: 0.764~0.851, P<0.01; OR=0.288, 95%CI: 0.189~0.439, P<0.01).

Conclusions

Low levels of HGF and VEGF contribute to the development of BPD. The levels of VEGF and HGF on the 3rd day after birth are connected with the development of BPD.

Key words: Bronchopulmonary dysplasia, Hepatocyte growth factor, Vascular endothelial growth factor, Infant, premature
表1 BPD组与非BPD组一般临床资料比较(±s)
Table 1 Comparison of clinical data between BPD group and BPD-free group (±s)
组别 例数 胎龄(孕周) 出生体质量(g) 性别[例数(%)] 绒毛膜羊膜炎[例数(%)] 妊娠期高血压综合征[例数(%)] 胎膜早破>24 h [例数(%)]
男性 女性
BPD组 22 29.1±1.8 1 324±322 14(63.6) 8(36.4) 8(36.4) 11(50.0) 7(31.8)
非BPD组 38 29.8±1.9 1 454±323 23(60.5) 15(39.5) 12(31.6) 15(39.5) 11(28.9)
t值/χ2值 ? 1.302 1.511 0.057 0.012 0.629 0.055 ?
P值 ? 0.315 0.323 0.811 0.913 0.428 0.815 ?
组别 产前用激素[例数(%)] 生后5 minApgar评分(分)a PS应用次数(次)a FiO2(%)a ? ? ? ?
BPD组 13(59.1) 9(3～10) 1(0～2.0) 40(35～60) ? ? ? ?
非BPD组 25(65.8) 9(8～10) 1(0～1.5) 40(34～50) ? ? ? ?
Z值/χ2值 0.269 0.105 1.902 0.843 ? ? ? ?
P值 0.604 0.708 0.056 0.394 ? ? ? ?
表2 BPD组与非BPD组BALF中HGF水平比较[pg/(mL·sIgA)，±s]
Table 2 Comparison of HGF levels in BALF between BPD group and BPD-free group[pg/(mL·sIgA)，±s]
组别 例数 HGF
第1天 第3天 第7天 第14天
BPD组 22 46.4±11.3 42.4±10.1 54.9±13.2 33.7±10.1
非BPD组 38 102.6±13.1 87.8±18.5 105.5±15.3 132.1±13.5
t值 13.829 12.200 8.686 14.063
P值 ? 0.000 0.000 0.000 0.000
表3 BPD组与非BPD组BALF中VEGF水平比较[pg/(mL·sIgA)，±s]
Table 3 Comparison of VEGF levels in BALF between BPD group and BPD-free group[pg/(mL·sIgA)，±s)]
组别 例数 VEGF
第1天 第3天 第7天 第14天
BPD组 22 4.9±2.9 20.7±4.8 48.4±9.6 51.4±8.5
非BPD组 28 21.6±3.8 33.9±6.8 73.1±6.8 58.6±8.7
t值 ? 19.254 8.686 7.257 1.464
P值 0.000 0.000 0.000 0.179
表4 第1，3，7天HGF和VEGF水平与BPD的二元非条件多因素logistic回归分析
Table 4 Logistic regression between BPD and level of HGF and VEGF on the 1st, 3rd, 7st day
自变量 B SE Wald OR值 95%CI P值
第1天 ? ? ? ? ? ?
? HGF －5.101 71.019 0.005 0.006 － 0.943
? VEGF －12.427 231.550 0.003 0.000 － 0.957
第3天 ? ? ? ? ? ?
? HGF －0.215 0.027 61.457 0.806 0.764～0.851 <0.001
? VEGF －1.245 0.216 33.315 0.288 0.189～0.439 <0.001
第7天 ? ? ? ? ? ?
? HGF －1.166 92.055 0.000 0.312 － 0.990
? VEGF －7.068 235.637 0.001 0.001 － 0.976
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