高体积分数氧致慢性肺疾病新生鼠肺泡II型上皮细胞超微结构的改变

摘要

目的 探讨高体积分数氧(高氧)损伤状态下,新生鼠肺组织通透性及肺泡Ⅱ型上皮细胞(AECⅡ)超微结构的动态变化.方法 新生大鼠320只,依据吸氧体积分数(FiO2)分组:实验组1(FiO2 800 mL·L-1)、实验组2(FiO2 600 mL·L-1)、实验组3(FiO2 400 mL·L-1)、空气对照组(FiO2 210 mL·L-1).每组分别于实验1 d、3 d、5 d、7 d、14 d取 8只鼠,计算其肺湿/干质量比值(W/D);另取8只新生鼠行支气管肺泡灌洗,检测其支气管肺泡灌洗液(BALF)中蛋白水平的动态变化; 透射电镜及硝酸镧示踪技术观察其AECⅡ超微结构及细胞膜通透性改变.结果 各实验组5 d、7 d、14 d肺W/D比值明显高于空气对照组,差异均有统计学意义(Pa<0.05),高氧3 d后实验组1与实验组2、实验组3的BALF中蛋白水平与空气对照组比较均显著增高(Pa<0.05);各实验组 7 d 内随暴露时间延长呈上升趋势;BALF 中蛋白水平在实验组3、实验组2、实验组1也呈逐渐增高趋势,且与空气对照组比较均显著增高(Pa<0.05).实验组AECⅡ的超微结构在出生后不同时间可以出现明显改变,且对硝酸镧颗粒通透性明显增加.结论 高氧肺损伤早期存在肺泡上皮通透性增加导致的肺水肿改变;新生鼠随着高氧暴露浓度的增高和时间的延长,肺损伤加重.%Objective To investigate the epithelial permeability in lung tissue and the ultrastructure dynamic changes of alveolar epithelia type Ⅱ cells ( AEC Ⅱ ) under hyperoxia - induced lung injury condition. Methods Three hundred and twenty cases of newborn rats were divided into 4 groups according to different oxygen concentrations ( FiO2 ): experimental group 1 ( FiO2 800 mL · L-1 ) ,experimental group 2 ( FiO2 600 mL · L-1 ) ,experimental group 3( FiO2 400 mL · L-1 ) and room - air control group ( FiO2 210 mL · L-1 ). Rats were killed on the 1st,3rd,5th,7th and 14th day after the onset of the experiment. The ultrastructures dynamic changes of AEC Ⅱ and alveolar barrier function through lanthanum nitrate tracing technology were observed. Lung wet/dry weight ratio(W/D) and protein content in bronchoalveolar lavage fluid (BALF) were examined. Results The lung W/D ratios in experimental groups were significantly higher than those in room - air control group on the 5th ,7th and 14th day of hyperoxia exposure( Pa ＜0.05 ). The protein contents of BALF in experimental groups were significantly higher than those in room- air control group( Pa ＜0.05 ) and increased as the oxygen concentration elevated and exposure time prolonged.The ultrastructures of AEC Ⅱ changed dramatically with longer exposure duration and the permeability of lanthanum nitrate in experimental groups were much higher than those in room - air control group. Conclusions Increased epithelial permeability which occurred at the early stage of hyperoxia - induced lung injury can lead to pulmonary edema;the lung injury became worse with higher oxygen concentration and longer exposure duration.