气管内一次性注入博莱霉素诱发大鼠肺损伤的动态变化

摘要

目的评估气管内一次性注入博莱霉素(bleomycin BLM)诱发大鼠肺纤维化病变最佳时间点.方法SD大鼠气管内一次性注入BLM,复制肺纤维化模型,对照组注入生理盐水,分别于7、14、28 d 1.5%戊巴比妥钠麻醉下,用肝素抗凝后注射器行腹主动脉抽血4ml,进行动脉血气分析.左肺行组织固定,右肺支气管肺泡灌洗,膜天平法进行肺表面物质(Puhonary surfactant,PS)活性测定.灌洗后右肺液氮速冻,进行羟脯氨酸(Hydroxyproline HYP)测定.结果7 d模型组动物出现明显低氧血症,14 d逐渐好转,但仍然低于正常,28d血氧饱和度完全恢复正常.其动态变化与体重、PS活性变化及病理组织切片的结果相一致.羟脯氨酸在14和28 d时明显增加,但两组间比较无明显差异.结论①气管内一次性注入BLM各指标变化最佳时间点在14 d.②博莱霉素通过损伤肺Ⅱ型细胞(ATⅡ),使PS系统功能异常,从而导致低氧血症的发生.%Objective: To assess the most suitable time point for a single intratracheal instillation (IT) of bleomycin-induced lung fibrosis model. Methods: SD rat were treated with a single IT dose of bleomycin or control saline. On days 7, 14 and 28 following IT bleomycin or saline instillation, animals were sacrificed under overdose of 1.5% sodium pentobarbital (0.25 ml/100 g, IP) and taken blood 4ml from the abdominal aorta with heparin-treated injection syringe for arterial blood gas analysis. The left lung was fixed for routine light microscopic examination.Bronchoalveolar lavage fluid (BALF) from the right lung was tested the activity of pulmonary surfactant (PS) by the whihelmy Film Balance, then the right lung was fromzen immediately in liquid nitrogen for determination of hydroxyproline concentration. Results: Model rats had obviously hypoxemia on days 7 and improved on days 14 and complete recovery to normal on days 28. This consecutive changes was coincident with changes of body weight, the activity of PS and tissue section pathological examination. Hydroxyproline levels increased in bleomycin-treated rats resulted in hypoxemia after bleomycin injured alveolar type Ⅱ (AT Ⅱ).