Huffman L J, Frazer D G, Prugh D J, Brumbaugh K, Platania C, Reynolds J S, Goldsmith W T
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
J Toxicol Environ Health A. 2004 Jan 23;67(2):125-44. doi: 10.1080/15287390490264776.
Evidence suggests that pregnant animals are more sensitive than nonpregnant animals to the systemic administration of endotoxin. Studies were undertaken to assess whether an enhanced sensitivity of the pulmonary system to aerosolized endotoxin might exist during pregnancy. Pregnant Sprague-Dawley female rats (17 d of gestation) or age-matched virgin female rats were exposed to air or endotoxin (lipopolysaccharide) by inhalation for 3 h. At 18 h following exposure to endotoxin, lactate dehydrogenase activity levels in bronchoalveolar lavage (BAL) fluid samples from pregnant rats were 1.5-fold greater than those from endotoxin-exposed virgin rats. BAL polymorphonuclear leukocyte (PMN) numbers were also approximately twofold greater in pregnant rats than in virgins following the inhalation of endotoxin. The increases in BAL PMNs in pregnant rats following endotoxin exposure were observed just following exposure to endotoxin as well as at 18 h following exposure. These results indicate that an increased pulmonary inflammatory response to inhaled endotoxin occurs during pregnancy in rats. Additional findings suggest that these pregnancy-linked pulmonary responses to endotoxin cannot be explained by the following potential mechanisms: changes in the inhaled dose of endotoxin, or alterations in the responsiveness of alveolar macrophages to endotoxin. To our knowledge this is the first study that has evaluated pulmonary responses to inhaled endotoxin during pregnancy. Our finding that pregnancy is associated with an increased lung inflammatory response to aerosolized endotoxin raises the possibility that there may be a generalized enhancement of pulmonary responses to inhaled toxic agents during pregnancy.
有证据表明，怀孕动物比未怀孕动物对内毒素的全身给药更为敏感。本研究旨在评估孕期肺部系统对雾化内毒素的敏感性是否增强。将怀孕的斯普拉-道来雌性大鼠（妊娠17天）或年龄匹配的未孕雌性大鼠通过吸入暴露于空气或内毒素（脂多糖）中3小时。暴露于内毒素后18小时，怀孕大鼠支气管肺泡灌洗（BAL）液样本中的乳酸脱氢酶活性水平比暴露于内毒素的未孕大鼠高1.5倍。吸入内毒素后，怀孕大鼠BAL中的多形核白细胞（PMN）数量也比未孕大鼠大约多两倍。在内毒素暴露后，怀孕大鼠BAL中PMN的增加在暴露后即刻以及暴露后18小时均有观察到。这些结果表明，大鼠在孕期对吸入内毒素的肺部炎症反应增强。其他研究结果表明，这些与妊娠相关的肺部对内毒素的反应不能通过以下潜在机制来解释：内毒素吸入剂量的变化，或肺泡巨噬细胞对内毒素反应性的改变。据我们所知，这是第一项评估孕期对吸入内毒素的肺部反应的研究。我们的发现，即妊娠与对雾化内毒素的肺部炎症反应增加有关，这增加了孕期对吸入有毒物质的肺部反应可能普遍增强的可能性。
