新生儿肺出血支气管肺泡灌洗液SP-A及TNF-α的变化及其相关性研究(英文)

目的近年研究发现急性肺损伤(ALI)是致新生儿肺出血的重要原因。大量研究表明肺表面活性蛋白A(SPA)和肿瘤坏死因子-α(TNFα)参与了ALI的损伤过程,但有关两者在肺出血新生儿支气管肺泡灌洗液(BALF)中的变化及关系鲜有报道。该研究旨在探讨SPA和TNFα在新生儿肺出血发生中的作用,两者间的关系及对预后的影响。方法采用斑点免疫印迹法和酶联免疫吸附法分别测定对照组(n=15),肺出血存活组急性期(n=14)、恢复期(n=14)和肺出血死亡组(n=6)新生儿BALF中SPA,TNFα和血清TNFα水平。结果存活组和死亡组新生儿肺出血急性期BALF中SPA含量(38.50±7.62,29.43±6.57)较对照组(44.88±7.48)显著降低(P=0.024,P=0),且死亡组SPA明显低于存活组急性期(P=0.015),存活组肺出血恢复期SPA水平(45.16±7.25)明显升高,接近对照组(P>0.05);而肺出血存活组和死亡组BALF中TNFα含量(208.54±64.69ng/L,319.16±46.79ng/L)较对照组(96.40±37.82ng/L)显著增加(P=0.011,P=0),死亡组比存活组急性期增加更明显(P=0),且BALF中TNFα的变化较血清中更明显,存活组恢复期BALF中TNFα水平(112.06±35.22ng/L)明显下降,接近对照组(P>0.05);肺出血患儿BALF中SPA水平的下降与TNFα的增高呈负相关(r=0.635,P=0.003)。结论SPA和TNFα参与了新生儿肺出血的肺损伤过程,为从SPA及细胞因子角度进一步认识新生儿肺出血的发病机制提供了实验依据,为新生儿肺出血的早期防治及预后判断提供了一种新的方法。

Levels of surfactant protein A and TNF-α in bronchoalveolar lavage fluid of newborns with pulmonary hemorrhage

Objective Recent studies have suggested that acute lung injury (ALI ) is an important cause of pulmonary hemorrhage of the newborn (PHN) and that surfactant protein A (SP-A) and tumor necrosis factor-α (TNF-α) are involved in the development of ALI. This study examined the levels of SPA and TNF-α in bronchoalveolar lavage fluid (BALF) and their relationship in newborns with pulmonary hemorrhage(PH). Methods Twenty newborn infants with PH and 15 sick neonates but without PH (Control group) were enrolled in this study. According to the prognosis, the PH group was subdivided into Survival group (n=14) and Death group (n=6). The Western-dot blot analysis and enzyme-linked immunoadsorbent assay (ELISA) were used to detect the levels of SP-A and TNF-α in BALF and serum TNF-α level. Results The SP-A levels in BALF in the survival PH patients in the acute stage and in the death PH cases were significantly lower than those of the Control group. The death PH patients showed a much lower SP-A level in BALF than the survival ones in the acute stage. Whilst the recovery stage of PH, the SP-A level in BALF in the survival patients increased significantly and remained the similar level as the Control group. The TNF-α levels in both serum and BALF in the survival PH patients in the acute stage and in the death PH cases were significantly higher than those in the Control group. The death PH cases showed a higher level of TNF-α in serum and BALF than PH survival cases in the acute stage. The increased extent of TNF-α level in BALF was obviously greater than of that in serum. In the recovery stage, the level of TNF-α in BALF was significantly reduced and almost returned to the level of the Control group in the survival PH cases compared with that in the acute stage. There was a negative correlation between the BALF SP-A and TNF-α levels in newborns with PH (r =-0.635,P = 0.003). Conclusions SP-A and TNF-α may be involved in the process of lung injury in PHN. Monitoring the levels of SP-A and TNF-α is useful for the early diagnosis and treatment and the evaluation of the outcome of PHN.