肺损伤生物学标志物检测对新生儿呼吸窘迫综合征的诊断价值

Diagnostic value of lung injury biomarkers in neonatal acute respiratory distress syndrome

目的探讨肺损伤生物学标志物E-选择素、Clara细胞蛋白(CC-16)、表面活性物质特异性蛋白-A(SP-A)检测在新生儿ARDS诊断中的作用。方法选择江苏省新生儿ARDS研究协作组9家医院于2015年3月1日至2016年2月29日收治的足月儿ARDS患儿为观察组,根据患儿肺氧合情况分成轻度、中度和重度,另外选择60例同期出生的正常足月新生儿作为对照组。观察组病例均在作出诊断的1、3、7 d采取静脉血标本,对照组新生儿均在生后7 d内采取,采用双抗体夹心酶联免疫法进行血浆E-选择素、血清CC-16和SP-A浓度检测。分析观察组患儿血液E-选择素、CC-16和SP-A浓度不同时间点的动态变化及不同严重程度ARDS患儿这几项指标的浓度变化,并进行相关性分析。结果观察组共纳入符合ARDS诊断标准新生儿60例,男38例、女22例,日龄(7.3±3.3)h,胎龄(39.5±1.7)周,出生体重(3280±577)g;对照组男30例、女30例,日龄(6.9±4.2)h,胎龄(39.4±1.5)周,出生体重(3329±593)g,两组比较差异无统计学意义(P>0.05)。观察组患儿血液E-选择素1 d、3 d、7 d分别为(36.36±8.32)μg/L、(45.51±9.26)μg/L、(17.15±6.84)μg/L;CC-161 d、3 d、7 d分别为(25.24±8.63)mg/L、(48.33±10.83)mg/L、(18.84±10.11)mg/L);SP-A 1 d、3 d、7 d分别为(58.38±10.31)mg/L、(63.29±11.31)mg/L、(25.99±6.66)mg/L,其浓度在发病第1天即出现升高,第3天达高峰,均较对照组[E-选择素、CC-16、SP-A分别为(15.52±6.24)μg/L、(11.26±5.18)mg/L、(24.30±5.27)mg/L]明显增高(P<0.05)。不同严重程度ARDS患儿血液E-选择素[轻度、中度、重度分别为(30.07±6.10)μg/L、(33.39±6.64)μg/L、(41.63±7.36)μg/L]、CC-16[轻度、中度、重度分别为(12.61±5.80)mg/L、(25.22±6.77)mg/L、(30.61±4.69)mg/L]和SP-A[轻度、中度、重度分别为(49.67±8.26)mg/L、(57.11±7.94)mg/L、(63.19±11.45)mg/L]浓度均逐渐增高,尤以中、重度增高明显。ARDS患儿血液中E-选择素(r=-0.6298)、CC-16(r=-0.6793)和SP-A(r=-0.4588)均与其PaO2/FiO2呈显著负相关(P<0.05)。结论ARDS患儿血液中E-选择素、CC-16和SP-A浓度显著升高,且与病情严重程度密切相关,可能成为新生儿肺损伤的生物学标志物。

Objective To investigate the role of E-selectin,Clara cell secretory protein 16(CC-16),and pulmonary surfactant protein A(SP-A)in the diagnosis of neonatal ARDS.Methods Full-term newborn with ARDS in 9 hospitals of Jiangsu Province from March 1st 2015 to February 29th 2016 were selected as observation group.According to the lung oxygenation of the neonates,they were divided into three groups:mild,moderate and severe.In addition,60 normal full-term newborns were selected as control group.In the observation group,venous blood samples were taken on the 1st,3rd and 7th day of diagnosis and the control group within 7 days after birth.The level of E-selectin,CC-16 and SP-A were detected by double antibody sandwich enzyme-linked immunosorbent assay.The changes of the level of E-selectin,CC-16 and SP-A at different time points and in neonatus with different severity of ARDS were compare with control group and correlatively analyzed.Results The observation group included 60 newborns who met the diagnostic criteria of ARDS with male 38,female 22,day age(7.3±3.3)hours,gestational age(39.5±1.7)weeks and birth weight(3280±577)g.The control group included 60 normal full-term newborns,with male 30,female 30,day age(6.9±4.2)hours,gestational age(39.4±1.5)weeks and birth weight(3329±593)g.There was no significant difference between two groups.The levels of E-selectin[1 d,3 d,7 d:(36.36±8.32)μg/L,(45.51±9.26)μg/L,(57.15±6.84)μg/L],CC-16[1 d,3 d,7 d:(25.24±8.63)mg/L,(48.33±10.83)mg/L,(18.84±10.11)mg/L]and SP-A[1 d,3 d,7 d:(58.38±10.31)mg/L,(53.29±11.31)mg/L,(25.99±6.66)mg/L]in the blood of the observation group increased on the first day and reached the peak on the third day,which were significantly higher than those in the control group[E-selectin,CC-16,SP-A:(15.52±6.24)μg/L,(11.26±5.18)mg/L,(24.30±5.27)mg/L](P<0.05).The levels of E-selectin[mild,moderate,severe are(30.07±6.10)μg/L,(33.39±6.64)μg/L,(41.63±7.36)μg/L],CC-16[mild,moderate,severe are(12.61±5.80)mg/L,(25.22±6.77)mg/L,(30.61±4.69)mg/L]and SP-A[mild,moderate,severe are(49.67±8.26)mg/L,(7.11±7.94)mg/L,(63.19±11.45)mg/L]increased gradually in the blood of ARDS neonates with different severity(P<0.05),especially in moderate and severe degree.There was a significant negative correlation between E-selectin(r=-0.6298),CC-16(r=-0.6793),SP-A(r=-0.4588)and PaO2/FiO2(P<0.05).Conclusion The levels of E-selectin,CC-16 and SP-A in the blood of ARDS neonates increased significantly and were closely related to the severity of the disease,which may be a biomarker of neonatal lung injury.