Blake T L, Reasor M J
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506-9223.
Inflammation. 1995 Feb;19(1):55-65. doi: 10.1007/BF01534380.
The use of the antiarrythmic drug amiodarone (AD) has been limited by the propensity of the drug to cause severe lung damage. AD has been shown to produce a transient pulmonary fibrosis in hamsters after intratracheal instillation. The goal of this study was to characterize the early inflammatory events associated with the administration of AD. Male Syrian hamsters that were instilled intratracheally with AD or saline vehicle underwent bronchoalveolar lavage (BAL). Total cells, macrophages, and eosinophils obtained by BAL were elevated by AD treatment at day 3. At both days 1 and 3 after instillation, AD-treated animals had significant elevations in neutrophil number. BAL fluid albumin was significantly elevated at day 1 in treated animals. Chemiluminescence (CL) performed on cells obtained by BAL showed an increase in CL of AD-treated samples compared to controls in phorbol myristate acetate (PMA) stimulated CL. PMA-induced increases in responsiveness were diminished by superoxide dismutase and catalase. These results indicate that oxidants such as superoxide and hydrogen peroxide may be involved in this inflammatory process. The results of this study show that intratracheal instillation of AD results in an inflammatory response that can be assessed by cellular, biochemical, and functional means.
抗心律失常药物胺碘酮（AD）的使用因该药物易导致严重肺损伤而受到限制。已表明，经气管内滴注后，AD可在仓鼠体内引起短暂性肺纤维化。本研究的目的是描述与AD给药相关的早期炎症事件。对经气管内滴注AD或生理盐水的雄性叙利亚仓鼠进行支气管肺泡灌洗（BAL）。在第3天，AD治疗使通过BAL获得的总细胞、巨噬细胞和嗜酸性粒细胞数量增加。在滴注后的第1天和第3天，接受AD治疗的动物中性粒细胞数量均显著增加。在第1天，接受治疗动物的BAL液白蛋白显著升高。对通过BAL获得的细胞进行的化学发光（CL）检测显示，与对照相比，在佛波酯肉豆蔻酸酯乙酸盐（PMA）刺激的CL中，AD处理样本的CL增加。超氧化物歧化酶和过氧化氢酶可减弱PMA诱导的反应性增加。这些结果表明，超氧化物和过氧化氢等氧化剂可能参与了这一炎症过程。本研究结果表明，经气管内滴注AD会导致炎症反应，可通过细胞、生化和功能手段进行评估。
