慢性肺部疾病患儿肺灌洗液中生物标记物的研究

Prediction of chronic lung disease with the biochemical markers in lung lavage fluid obtained from ventilated neonates

目的研究机械通气患儿肺灌洗液中生物标志物的变化,以探讨其在早期诊断早产儿慢性肺部疾病中的意义。方法将1999年12月至2004年8月在NICU行机械通气>5d的71例新生儿按原发疾病分为4组:肺炎组(21例)、肺透明膜病组(RDS组,16例)、慢性肺部疾病组(CLD组,19例)、对照组(15例)。所有患儿对肺灌洗液行细胞学检验;采用比色法检测灌洗液中丙二醛(MDA)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)含量;采用放免法对灌洗液中TNF-α、IL-8、IL-1和IL-6及内皮素-1(ET-1)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)和羟脯氨酸(Hyp)含量进行检测。数据统计采用K-W检验。结果①生后4d内四组间各检测值比较差异无统计学意义,生后第5天差异有统计学意义。②生后第5天CLD组肺灌洗液中总蛋白(75.4g/L)及MDA(39.39nmol/ml)较非CLD组明显增加(P<0.05),SOD(8.03U/ml)及GSH(795mg/L)显著下降(P<0.05);③CLD组生后第5天肺灌洗液中的TNF-α(7.62fmol/ml)、IL-8(376.9mg/ml)、IL-1(2.09ng/ml)、IL-6(1.02ng/ml)、ET-1(2.66ng/ml)、PCⅢ(110.82μg/ml)、HA(258.65mg/ml)和Hyp(12.03ng/ml)均明显高于其他三组(P<0.05)。结论CLD的发生为一复杂过程,生后第5天肺灌洗液中各生物标志物水平对早期诊断早产儿慢性肺部疾病有重要意义。

Objectives To investigate the changes of specific biochemical markers in lung lavage fluid from ventilated infants with and without chronic lung diseases （CLD）, and explore the early diagnostic significance of in premature infants with CLD. Methods A total of 71 infants who received mechanical ventilation from Dec 1999 to Sep 2004 were enrolled in this study. The babies were divided into 4 groups： CLD （19 cases）, RDS （16 cases）, pneumonia （21 cases） and control （15 cases） . Malondialdehyde （MDA）, superoxide dismutase （SOD）, and glutathione （GSH） were measured with colorimetric method. Tumor necrosis factor （TNF-α）, interleukin （IL-8, IL-1, IL-6）, endothelin （ET-1）, procollagen （PCo）, hyaluronic acid （HA）, and hydroxyproline （Hyp） were detected with radioimmunoassay. The results were analyzed by using K-W test. Results There was no significant difference between the 4 groups in the first 4 days of life, while on day 5 of age, a significant difference was detected. On day 5, total protein （median 75.4 g/L）, MDA （median 39.39 nmol/ml） were increased while SOD （median 8.03 U/ml） and GSH （median 795 mg/L） were decreased in lung lavage fluid in the CLD group in comparison with the other 3 groups （P 〈 0.05）. Also on Day 5, the levels of TNF-α （median 7.62 fmol/ml）, IL-8 （median 376.9 mg/ml）, IL-1 （median 2.09 ng/ ml） and IL-6 （median 1.02 ng/ml）, ET-1 （median 2.66 ng/ml）, PCⅢ （median 110.82 ug/ml）, HA （median 258.65 mg/ml） and Hyp （median 12.03 ng/ml） in CLD group were higher than those in others 3 groups （P 〈 0.05）. Conclusions The development of CLD is a complex process. Since specific biochemical markers could be identified on day 5 in infants who developed CLD, they may have an important role in the pathogenesis of CLD.