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

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

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。

Abstract:

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.