急性和慢性肺损伤的模式及病因:基于非临床性实验证据的剖析(英文)  

Patterns and etiology of acute and chronic lung injury: insights from experimental evidence

作　　者：Matthias C. Hutten Boris W. Kramer 

机构地区：[1]Department of Pediatrics/Neonatology, University Clinic RWTH Aachen, Germany [2]Department of Pediatrics/Neonatology, Maastricht University Medical Center, The Netherlands

出　　处：《中国当代儿科杂志》2014年第5期448-459,共12页Chinese Journal of Contemporary Pediatrics

摘　　要：满足最基本需求的肺功能是早产儿存活的先决条件。早产儿肺结构和功能欠成熟,常常伴发呼吸窘迫综合征(RDS)。除结构不成熟之外,早产儿肺组织还易因出生前后各种不利状况及因素而受损,进而防碍生后肺部的正常发育,促发非成熟性慢性肺部病变,导致支气管肺发育不良(BPD)。该文将以由炎症变化而引发并与炎症变化密切相关的肺损伤为重点,全面综述用以探讨早产儿肺部炎症反应机制的各种实验模型,这其中包括用来研究绒毛膜羊膜炎发病机制的模型。人们知道,绒毛膜羊膜炎与早产密切关。从临床角度讲,胎儿宫内接触绒毛膜羊膜炎会导致胎儿肺组织发育异常,进而影响早产儿的肺功能。根据临床数据,有作者认为:暴露于绒毛膜羊膜炎的胎儿其支气管肺发育不良的风险增高,但RDS的风险反而降低。目前有实验数据表明,急性和慢性羊膜炎均可导致胎儿肺部炎症反应。一些研究人员建立了各种动物模型,他们除了借助这些模型来检测肺组织中诸如IL-1之类炎症介质的水平外,他们还用这些模型研究过炎症介质在肺发育成熟过程中的作用。在接触过宫内炎症的动物胎儿,肺组织磷脂酰胆碱的生成量及表面活性蛋白的水平增高,这表明脂酰胆碱表面活性蛋白会影响肺上皮细胞成熟,其影响程度之大小主要取决于暴露炎症因子的时间和剂量以及炎症因子的性质。使用细菌脂多糖(LPS)或解脲活性物作为炎症因子处理实验动物可以模拟人绒毛膜羊膜炎的临床表现。此外,实验数据表明,胎儿似乎具有抗衡并降低炎症反应程度的能力。目前,越来越多的证据表明抗逆内毒素是胎儿炎症调节的一个重要机制。产前用糖皮质激素(GCS)处理孕妇是早产的标准治疗方案,该处理可对胎儿肺组织和免疫细胞的成熟施以复杂的影响。有趣的是,GCS对肺形态和功能的作用与LPS诱导�Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia （BPD）. This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids （GCS）. New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects.

关 键 词：慢性肺损伤 实验模型 非临床 炎症反应机制 支气管肺发育不良 呼吸窘迫综合征 证据 病因 

分 类 号：R979.9[医药卫生—药品]