Hybertson B M, Lee Y M, Cho H G, Cho O J, Repine J E
Webb-Waring Institute for Cancer, Aging, and Antioxidant Research, Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Inflammation. 2000 Aug;24(4):289-303. doi: 10.1023/a:1007092529261.
Acute lung injury (ALI) is characterized by increased lung levels of proinflammatory cytokines, inflammation, oxidative stress, edema, and impaired gas exchange. Notably, ALI patients also exhibit pulmonary surfactant abnormalities, including increased levels of phospholipids in their lung lavages. In the present study, to assess early alterations of the lung surfactant system in ALI, we induced inflammation and acute lung injury in rats by administering interleukin-1alpha (IL-1) intratracheally. Five h after IL-1 instillation, we examined lung tissue ultrastructure by electron microscopy using both routine staining methods and cerium chloride staining to localize hydrogen peroxide (H2O2) histologically. We also measured lung lavage phospholipid levels, lung tissue gamma-glutamyl transpeptidase (GGT) activities (a marker of oxidative stress), and arterial blood oxygen tensions. We observed that lungs of rats given IL-1 intratracheally had increased neutrophil accumulation, increased H2O2 production, and increased alveolar type II (ATII) pneumocyte ultrastructural abnormalities compared to rats given saline intratracheally. Intratracheal instillation of IL-1 also increased phospholipid levels in the bronchoalveolar lavage (BAL), possibly as a consequence of the abnormal discharge of lamellar bodies into the alveolar lumen. In addition, IL-1-insuffated rats had increased lung GGT levels and impaired blood oxygenation compared to saline-insufflated rats. Treatment with mepacrine decreased lung neutrophil accumulation, ultrastructural lung abnormalities, lung lavage phospholipid levels, lung tissue GGT levels, and blood oxygenation impairment in rats given IL-1 intratracheally, suggesting a possible relationship between these events. Our results indicate that IL-1-induced acute lung injury in rats is marked by neutrophil-dependent oxidative stress, ATII cell defects, abnormal discharge of lamellar body phospholipids, and impaired blood oxygenation.
急性肺损伤（ALI）的特征是肺内促炎细胞因子水平升高、炎症、氧化应激、水肿以及气体交换受损。值得注意的是，ALI患者还表现出肺表面活性物质异常，包括肺灌洗液中磷脂水平升高。在本研究中，为了评估ALI中肺表面活性物质系统的早期变化，我们通过气管内给予白细胞介素-1α（IL-1）在大鼠中诱导炎症和急性肺损伤。在滴注IL-1后5小时，我们使用常规染色方法和氯化铈染色通过电子显微镜检查肺组织超微结构，以组织学定位过氧化氢（H2O2）。我们还测量了肺灌洗磷脂水平、肺组织γ-谷氨酰转肽酶（GGT）活性（氧化应激的标志物）以及动脉血氧张力。我们观察到，与气管内给予生理盐水的大鼠相比，气管内给予IL-1的大鼠肺内中性粒细胞积聚增加、H2O2产生增加以及肺泡II型（ATII）肺上皮细胞超微结构异常增加。气管内滴注IL-1还增加了支气管肺泡灌洗（BAL）中的磷脂水平，这可能是板层小体异常释放到肺泡腔中的结果。此外，与给予生理盐水的大鼠相比，给予IL-1的大鼠肺GGT水平升高且血液氧合受损。用米帕林治疗可减少气管内给予IL-1的大鼠的肺中性粒细胞积聚、肺超微结构异常、肺灌洗磷脂水平、肺组织GGT水平以及血液氧合损伤，提示这些事件之间可能存在关联。我们的结果表明，IL-1诱导的大鼠急性肺损伤的特征是中性粒细胞依赖性氧化应激、ATII细胞缺陷、板层体磷脂异常释放以及血液氧合受损。
