动态监测早产儿支气管肺泡灌洗液中β-联蛋白、转化生长因子β1、Clara细胞分泌蛋白16、Ⅱ型肺泡细胞表面抗原6水平变化的意义

The significance of detecting the changes of β-catenin,transforming growth factor-β1, Clara cell secretion protein 16, Krebs von den Lungen-6 level in bronchoalveolar lavage fluid of premature children

目的 探讨早产儿支气管肺泡灌洗液（BALF）中β-联蛋白、转化生长因子β1（TGF-β1）、Clara细胞分泌蛋白16（cc16）、Ⅱ型肺泡细胞表面抗原6（KL-6）水平动态变化在机械通气肺损伤乃至支气管肺发育不良（BPD）中的意义.方法 选择机械通气早产儿60例,将30例诊断为BPD的患儿作为试验组,30例非BPD患儿作为对照组,酶联免疫吸附试验（ELISA）法测定机械通气后所有患儿1,24,48,72 h BALF中β-联蛋白、TGF-β1、cc16、KL-6水平.结果 试验组患儿胎龄及出生体质量明显低于对照组,吸氧时间及机械通气时间明显长于对照组,差异均有统计学意义（P＜0.01）.随着机械通气时间的延长,试验组BALF中β-联蛋白、TGF-β1、KL-6水平呈逐渐升高趋势,cc16水平呈逐渐降低趋势,且机械通气48,72 h后与机械通气1h后比较差异有统计学意义[（304.64±64.84）,（358.39±61.81） ng/L比（251.84±59.51） ng/L; （305.6±76.4）,（380.8±88.3） μgL比（200.5±63.8）μg/L; （972.6±232.0）,（1 114.8±253.1） U/L比（822.2±239.9） U/L;（69.92±12.37）,（57.46±12.22）μg/L比（83.24±15.41）μg/L]（P＜ 0.05）.对照组cc16、TGF-β 1机械通气72 h后与机械通气1h后比较差异有统计学意义[（84.08±19.90） μg/L比（106.90±30.58） μg/L,（185.2±75.3） μg/L比（137.5±59.1） μg/L]（P＜0.01）,而KL-6、β-联蛋白各机械通气时段比较差异无统计学意义（P＞0.05）.试验组各机械通气时段TGF-β1、β-联蛋白水平均高于对照组、cc16水平均低于对照组,而KL-6水平机械通气48,72 h后高于对照组,差异均有统计学意义（P＜0.01）.Pearson分析结果显示,机械通气1h后BALF中TGF-β1与胎龄呈负相关（r=-0.274,P＜ 0.05）,cc16与体质量呈正相关（r=0.375,P＜0.01）,β-联蛋白与体质量呈负相关（r=-0.414,P＜0.01）,β-联蛋白与cc16呈负相关（r=-0.248,P＜0.05）,与TGF-β1呈正相关（r=0.290,P＜0.05）.多元逐步回归分析提示,机械通气、吸氧时间的延长、低1 h BALF中cc16水平是BPD发生的高危因素（P＜0.01）.结论 通气初始（通气1 h）BALF中,高TGF-β1、高β-联蛋白、低cc16水平与早产儿低胎龄、低出生体质量密切相关,而通气48 h后BALF中持续显著升高的KL-6、β-联蛋白、TGF-β1水平与持续显著降低的cc16水平,有助于监测机械通气肺损伤乃至BPD的发生发展.

Objective To investigate the significance of β-catenin,transforming growth factor-β 1 （TGF-β 1）,Clara cell secretion protein 16 （cc16）,Krebs von den Lungen-6 （KL-6） level changes in bronchoalveolar lavage fluid （BALF） of premature for mechanical ventilation lung injury and bronchopulmonary dysplasia （BPD）.Methods Selected 60 mechanical ventilation preterm infants,basing on the BPD diagnosis criterion that the United States national institutes of health research joint BPD team released in 2001,30 BPD children were disposed as experimental group,other 30 non-BPD children as control group.The levels of β-catenin,KL-6,cc16,TGF-β1 in BALF were measured by enzyme-linked immunosorbent assay（ELISA） after mechanical ventilation 1,24,48,72 h.Results The gestational age and body mass in experimental group were significantly lower than those in control group （P〈 0.01）,the time of mechanical ventilation and oxygen inhalation was significantly longer than that in control group （P 〈 0.01）.The levels of β-catenin,TGF-β 1,KL-6 in 48,72 h after mechanical ventilation in experimental group were significantly higher than those of 1 h [（304.64 ± 64.84）,（358.39 ± 61.81） ng/L vs.（251.84 ± 59.51） ng/L; （305.6 ± 76.4）,（380.8 ± 88.3） μ g/L vs.（200.5 ± 63.8） μ g/L; （972.6 ± 232.0）,（1 114.8 ± 253.1） U/L vs.（822.2 ± 239.9） U/L]（P〈 0.05）,the level of cc16 was significantly lower than that of 1 h[（69.92 ± 12.37）,（57.46 ± 12.22） μg/L vs.（83.24 ± 15.41） μg/L]（P〈 0.05）.The differences of levels ofcc16,TGF-β 1were significant between 72 h and 1 h after mechanical ventilation [（84.08 ± 19.90） μ g/L vs.（106.90 ± 30.58） μg/L,（185.2 ±75.3） μg/L vs.（137.5 ±59.1）μg/L] （P 〈0.01）,the difference of KL-6,β-catenin in various mechanical ventilation time was not statistically significant （P 〉 0.05）.The levels of TGF-β,β-catenin in various mechanical ventilation time in experimental group were significantly higher than those in control group （P 〈 0.01）,the level of cc16 was significantly lower than that in control group （P〈 0.01）,the levels in 48,72 h of KL-6 after mechanical ventilation were significantly higher than those in control group （P〈 0.01）.Pearson analysis showed that,1 h after mechanical ventilation,TGF-β 1 negatively correlated with gestational age （r =-0.274,P 〈 0.05）,cc 16 positively correlated with body mass （r =0.375,P 〈 0.01）,β-catenin negatively correlated with body mass （r =-0.414,P 〈 0.01）,β-catenin negatively correlated with cc 16 （r =-0.248,P 〈 0.05）,β-catenin negatively correlated with TGF-β 1 （r =0.290,P 〈0.05）.Multiple stepwise regression analysis indicated that,mechanical ventilation,longer time of oxygen inhahtion,lower level of 1 h BALF and cc16 were risk factors for the occurrence of BPD （P 〈 0.01）.Conclusions Higher TGF-β 1,β-catenin and lower cc16 levels of BALF in 1 h after ventilation are closely related to gestational age and body mass,while after being ventilated for 48 h,higher KL-6,β-catenin,TGF-β 1 and lower cc16 level of BALF in infants are helpful to monitor the mechanical ventilation lung injury and the development of BPD.