Wang S, Lantz R C, Chen G J, Breceda V, Rider E, Hays A M, Parliman G, Tollinger B J, Robledo R F, Kunke K, Tinajero J, Witten M L
Department of Paediatrics, Steele Memorial Children's Research Center, Tucson, Arizona, USA.
Pharmacol Toxicol. 1996 Nov;79(5):231-7. doi: 10.1111/j.1600-0773.1996.tb00265.x.
The effects of the lazaroid analogue U75412E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9]-(11)-triene-3,20-dione) were examined in an acute lung injury rabbit model. Standard doses of 0, 8 and 16 mM U75412E were aerosolized and ventilated into the lungs for 3 min. via an endotracheal tube. A 60 tidal volume dose of diesel fuel-polycarbonate plastic smoke was then instilled, followed by mechanical ventilation for one hour. Pretreatment with 16 mM U75412E significantly increased blood PaO2 and pH values, and decreased blood PaCO2 as compared to smoke only exposures. It also significantly decreased the total cell counts and granulocytes in bronchoalveolar lavage fluid, and the ability of pulmonary alveolar macrophages to produce tumour necrosis factor-alpha in vitro after cell isolation and culture. Histopathology indicated that 16 mM U75412E pretreatment attenuated increases in wet lung/body weight ratios, inflammatory focus, and interstitial oedema associated with smoke insult. In summary, U75412E pretreatment may possess the potential to improve acute smoke-induced lung injury, in part, through modulation of tumour necrosis factor-alpha production from pulmonary alveolar macrophages.
在急性肺损伤兔模型中研究了类拉扎罗类化合物U75412E（21-[4-(3-乙氨基-2-吡啶基)-1-哌嗪基]-16α-甲基孕甾-1,4,9(11)-三烯-3,20-二酮）的作用。将0、8和16 mM的标准剂量U75412E雾化，通过气管内导管通气至肺内3分钟。然后注入60潮气量剂量的柴油-聚碳酸酯塑料烟雾，随后进行1小时的机械通气。与仅暴露于烟雾的情况相比，用16 mM U75412E预处理可显著提高血液中的PaO2和pH值，并降低血液中的PaCO2。它还显著降低支气管肺泡灌洗液中的总细胞计数和粒细胞数量，以及肺泡巨噬细胞在细胞分离和培养后体外产生肿瘤坏死因子-α的能力。组织病理学表明，16 mM U75412E预处理可减轻与烟雾损伤相关的湿肺/体重比增加、炎症灶和间质水肿。总之，U75412E预处理可能具有改善急性烟雾诱导的肺损伤的潜力，部分是通过调节肺泡巨噬细胞产生肿瘤坏死因子-α来实现的。
