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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(Pulmonary 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,28 d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 evaluate the best time point of pulmonary fibrosis induced by bleomycin BLM in the trachea. Methods BLM was injected intratracheally into the trachea of SD rats and the model of pulmonary fibrosis was duplicated. The control group was infused with normal saline, and anesthetized with pentobarbital sodium 1.5% Arterial blood 4ml, arterial blood gas analysis. Left lung tissue was fixed, right lung bronchoalveolar lavage, membrane balance method for determination of Pulmonary surfactant (PS) activity. After lavage, the right lungs were rapidly frozen in liquid nitrogen for determination of Hydroxyproline HYP. Results On the 7th day, the animals in the model group showed obvious hypoxemia, gradually improved on the 14th day, but still below the normal level. The blood oxygen saturation completely returned to normal on the 28th day. Its dynamic changes and weight, PS activity changes and pathological tissue sections consistent. Hydroxyproline increased significantly at 14 and 28 days, but there was no significant difference between the two groups. Conclusion ① The best time point for all indexes of BLM injected into the trachea is 14 days. ② bleomycin through the injury of lung Ⅱ type cells (AT Ⅱ), PS system dysfunction, resulting in the occurrence of hypoxemia.