中文摘要：

目的动态观察高氧暴露新生早产大鼠肺组织肺泡上皮细胞（AEC）超微结构与细胞外基质（ECM）的变化，探讨其在高氧性肺损伤肺纤维化发病机制中的作用。方法将80只新生早产SD大鼠随机分为空气组和高氧组，空气组在空气中饲养，高氧组置于高氧箱（保持氧体积分数〉950 ml／L）中饲养，每组40只；每组又随机分为3、7、14、21 d 4个亚组，每组10只。分别在第3、7、14、21天处死动物，收集肺组织标本。采用透射电镜观察各亚组大鼠AEC超微结构改变；采用碱水解法测定其肺组织匀浆羟脯氨酸（HYP）含量；采用免疫组织化学方法检测肺组织Ⅰ型与Ⅲ型胶原表达与分布；并用图像分析方法检测肺组织Ⅰ、Ⅲ型胶原阳性表达的PU值。结果高氧组第3天即出现AEC轻度损伤；第7天时AEC损伤加重，第14、21天时出现AEC—Ⅱ坏死，板层小体基本排空，AEC基底膜及气血屏障明显增厚，肺间质可见大量胶原原纤维。肺组织HYP含量随着高氧暴露时间的延长而逐渐增加，第21天时达最高，在第7、14、21天时均明显高于空气组。Ⅰ、Ⅲ型胶原均在第3天呈弱阳性表达，第14、21天呈强阳性表达。肺组织Ⅰ、Ⅲ型胶原阳性表达的PU值在第14、21天时明显高于空气组（P〈0．01）。结论AEC损伤是早产大鼠长时间高氧暴露所致肺损伤的早期特征，而后期以肺间质ECM过度沉积为主。

英文摘要：

Objective To study the role of alveolar epithelial cell （AEC） injury in pulmonary fibrosis in hyperoxia-exposed premature newborn rats. Methods 80 premature newborn SD rats （GA = 21 d） were randomly assigned into air group and hyperoxie group （n = 40）, the rats in each group were randomly divided into four subgroups, 3 d,7 d, 14 d and 21 d （n = 10）. The rats in air groups were kept in air and rats in hyperoxic groups were kept in hyperoxic chamber （with a constant oxygen flow of 950 ml/L）. The ultrastructural changes of lung tissues of rats were observed by transmission electron microscope; the measurement of hydroxyproline in lung homogenates was analyzed by alkali hydrolyzation. Immunohistochemical methods were applied in detecting expression and distribution of type Ⅰ and type Ⅲ collagens in lung tissue of premature rats in various subgroups. Image analysis was used to measure PU values of positively expressed type Ⅰ and type Ⅲ collagens in lung tissue. Results It was observed that mild AEC injury and neutrophilic leukocytes infiltration of lungs of rats in hyperoxic groups on day 3. AEC injure became more severe on dav 7 ： necrosis of AEC -Ⅱ , thickening of the basement membrane and air-blood barrier of ACEs, deposition of collagen fibril in lung interstitium were observed on day 14 and 21 of rats in the hyperoxic groups. The content of hydroxyproline in lung homogenates increased with prolonged exposure of hyperoxia and peaked on day 21, it was significantly higher for rats in hyperoxic groups than those in air group on day 7,14 and 21 respectively. The expression of type Ⅰ collagen was weakly positive on day 3 and day 7 and it became strongly positive on day 14 and day 21 ; the level of expression began to increase from day 14 and peaked on day 21. The expression of type Ⅲ collagen on day 3 was weakly positive, it became moderately positive on day 7 and turned strongly positive on day 14 and 21 ; the level of expression began to rise on day 7 and peaked on day 14, the lev