小窝蛋白-1在早产鼠高体积分数氧肺损伤中的表达及其意义

Expression of Caveolin-1 in Lung of Premature Rats with Hyperoxia-Induced Chronic Lung Disease and Its Significance

目的研究高体积分数氧(高氧)肺损伤早产鼠肺组织小窝蛋白-1的动态表达及其与肺纤维化的关系。方法剖宫术取出孕21 d大鼠作为早产鼠,30只新生早产W istar大鼠生后12 h随机分为高氧组和对照组,每组15只,高氧组持续暴露于950 mL.L-1氧气中,空气组置于同一室内常压空气中。分别于暴露1 d、3 d、7 d时,每组取动物5只,留取其肺组织标本,常规制成5μm切片,应用HE染色观察不同时间点其肺组织病理改变,在光镜下进行肺组织纤维化评分,并采用免疫组织化学法检测不同时间点其肺组织小窝蛋白-1的表达部位和强度,将小窝蛋白-1的表达与肺纤维化进行相关性分析。结果早产鼠高氧暴露3 d后出现明显急性炎症改变,肺泡内有出血和炎性细胞浸润,间质纤维化,且病变随高氧暴露时间的延长而加重;小窝蛋白-1在对照组早产大鼠肺组织中均有较高水平表达,高氧组早产鼠吸入高氧1 d,肺组织小窝表达出现降低,在3 d、7 d明显降低,与对照组比较差异均有统计学意义(Pa<0.05),尤以高氧7 d最明显;小窝蛋白-1与纤维化评分呈负相关(Pa<0.05)。结论高氧诱导急性肺损伤,导致早产鼠肺组织小窝蛋白-1表达持续性减少,其异常表达可能是导致肺成纤维细胞过度增殖,最终发生肺间质纤维化的重要原因。实用儿科临床杂志,2011,26(12)

Objective To explore the dynamic expression of caveolin-1 in lung of premature rats exposed to hyperoxia and the relationship between caveolin-1 and pulmonary fibrosis.Methods Thirty premature Wistar rats at 21 days gestation were randomly and equally divided into hyperoxia group and room air group.Hyperoxia group was continuously exposed to 950 mL·L-1 oxygen and air group in room air.The lung tissues in 2 groups were obtained at 1,3 and 7 days after exposing to either room air or hyperoxia.Lung tissues were collected and made into 5 μm sections.The changes of pulmonary histopathology of different time points were observed by hematoxylin and eosin staining,the severity of pulmonary fibrosis was evaluated,and the expression of caveolin-1 in lung tissue was detected by immunohistochemistry.Results After 3 days of hyperoxia,in hyperoxia-model group,hemorrhage and inflammatory cell infiltration in lung alveoli were observed,and interstitial fibrosis were observed.These changes became more obvious with more prolonged hyperoxia exposure.Expression of caveolin-1 remained at a higher level in control group.Caveolin-1 expression in hyperoxia exposure group was decreased from 1 day,markedly at 3 days and 7 days（Pa0.05） compared with the controls,and the expression of caveolin-1 was negatively correlated with score of interstitial fibrosis in lung（Pa0.05）.Conclusions Hyperoxia can induce acute lung injury as well as progressive reduction in lung caveolin-1 expression.The abnormal expression of caveolin-1 might result in over-proliferation of lung fibroblast,which ultimately develops into interstitial fibrosis in lung.