低氧条件下急性肺损伤小鼠肺血管通透性变化

Hypoxia Oxygen Changes Lipopolysaccharide-induced Pulmonary Vascular Permeability in Mice

目的:观察低氧环境下急性肺损伤(ALI)小鼠肺水含量、组织病理学及血管通透性变化,探讨低氧环境下ALI致死的可能机制。方法:280只昆明白小鼠,分为常氧+PBS组(CK组,n=35)、低氧+PBS组(HP组,n=35)、常氧+内毒素(LPS)组(NL组,n=60)和低氧+LPS组(HL组,n=150)。NL组和HL组采用LPS诱导致ALI模型,CK组和HP组给予等量PBS,随后按分组要求分别于常氧条件和低压氧仓中饲养,于造模后第1、3、7天观察各组小鼠肺水含量、肺组织病理学评分、肺血管通透性等指标变化,同时观察各组小鼠7天内的存活率,并比较分析各组差异。结果:与其它三组比较,HL组小鼠实验7天后死亡率明显增加(P<0.05);在LPS所致ALI后,HL组肺水含量显著高于NL组(P<0.05);肺组织HE染色结果显示,HL组出现较为严重的肺间质水肿、肺泡腔缩小、血管肥大、肺间质增厚等病理变化,且肺组织中伊文思蓝含量在第7天显著高于NL组(P<0.01)。结论:低氧条件下ALI死亡率增加可能与肺间质屏障功能受损及肺血管通透性增加有关。

Objective： To investigate the effects of hypoxia on acute lung injury（ALI） from pulmonary vascular permeability perspective and analyze the possible mechanism of ALI death in hypoxic environment. Method： 280 kunming white mice were divided into normoxia＋PBS group （CK group,n=35）, hypoxia＋PBS group （HP group,n=35）, normoxia＋LPS group （NL group, n=60） and hypoxia＋LPS group （HL group,n=150）.NL group and HL group were induced ALI by LPS, combination of CK and HP group were given amount of PBS, then breeding the mice in normoxia and hypoxia conditions according to the requirements. Lung moisture content, lung pathological score, change of the pulmonary vascular permeability in different time for 1st,3rd,7th day after injury, at the same time the survival rate at 7th day were observed, and compared the differences among groups. Results： Compared with the other three groups, the mortality of HL group was significantly increased after 7th day （P〈0.05）. After LPS induced ALI, the lung moisture content in HL group was significantly higher than that in NL group （P〈0.05）. At the same time, the pathological section, according to a set of HL group appeared more severe lung interstitial edema, alveolar space decreased, vascular hypertrophy, and thickening of pulmonary interstitium and Evans blue content in lung tissue at 7th day was significantly higher than NL group （P〈0.01）. Conclusion： The increase of ALI mortality under hypoxic conditions may be related to the impaired function of pulmonary interstitial barrier and increased pulmonary vascular permeability under hypoxic conditions.