Witten M L, Quan S F, Sobonya R E, Bruck D, Devine L, Lemen R J
Department of Physiology, University of Arizona College of Medicine, Tucson.
Exp Lung Res. 1988;14(6):727-42. doi: 10.3109/01902148809087840.
We studied lung clearance of technetium-labeled diethylenetriamine pentaacetic acid [( 99mTc]DTPA), plasma and bronchoalveolar lavage fluid (BALF) concentrations of 6-keto-PGF1 alpha (stable metabolite of prostacyclin, prostaglandin I2, PGI2), TxB2 (stable metabolite of thromboxane A2, TxA2), and leukotriene B4 (LTB4), and inflammatory cells as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Thirty-one rabbits were randomly assigned to four groups: control sham exposure (SS, n = 6), sham smoke ibuprofen-pretreated (SS-I, n = 7), CSE (n = 6), and CSE ibuprofen-pretreated (CSE-I, n = 12). Ibuprofen, a cyclooxygenase eicosanoid inhibitor, was administered as a single daily intramuscular injection (25 mg/kg) for 7 d before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine [99mTc]DTPA biological half-life (T1/2). The CSE-I group was retrospectively divided into rabbits who survived the 30-breath subset (CSE-IL, n = 6) and those who died during the 30-breath CSE (CSE-ID, n = 6). In the CSE, CSE-IL, and CSE-ID groups, [99mTc]DTPA T1/2 as well as BALF LTB4 levels were significantly decreased. Plasma and BALF 6-keto-PGF1 alpha increased in CSE rabbits compared to the other groups. Alveolar macrophages were lower in the CSE-ID rabbits than in the CSE-IL group. CSE and CSE-IL BALF lymphocyte levels were decreased compared to SS values. Our data indicate that acute CSE is associated with significant increases in 6-keto-PGF1 alpha and decreases in LTB4 as well as a significant reduction in lymphocytes. Furthermore, pretreatment with ibuprofen before CSE was associated with severe lung injury in half of the rabbits. The severity of lung injury may be related to a combination of a lower number of alveolar macrophages and blockade of lung PGI2.
我们研究了用锝标记的二乙烯三胺五乙酸[（99mTc）DTPA]的肺清除率、血浆和支气管肺泡灌洗液（BALF）中6-酮-前列环素F1α（前列环素、前列腺素I2、PGI2的稳定代谢产物）、血栓素B2（血栓素A2、TxA2的稳定代谢产物）和白三烯B4（LTB4）的浓度，以及作为暴露于香烟烟雾（CSE）的兔肺损伤指标的炎性细胞。31只兔被随机分为四组：对照假暴露组（SS，n = 6）、假吸烟布洛芬预处理组（SS-I，n = 7）、CSE组（n = 6）和CSE布洛芬预处理组（CSE-I，n = 12）。布洛芬是一种环氧化酶类花生四烯酸抑制剂，在实验前连续7天每天单次肌肉注射（25 mg/kg）。通过注射器以一系列5次、10次、20次和30次潮气量呼吸给予香烟或假吸烟，每次呼吸子集之间有15分钟的计数期以确定[99mTc]DTPA生物半衰期（T1/2）。CSE-I组回顾性地分为在30次呼吸子集存活的兔（CSE-IL，n = 6）和在30次呼吸CSE期间死亡的兔（CSE-ID，n = 6）。在CSE、CSE-IL和CSE-ID组中，[99mTc]DTPA T1/2以及BALF LTB4水平显著降低。与其他组相比，CSE兔的血浆和BALF 6-酮-前列环素F1α升高。CSE-ID兔的肺泡巨噬细胞低于CSE-IL组。与SS值相比，CSE和CSE-IL的BALF淋巴细胞水平降低。我们的数据表明，急性CSE与6-酮-前列环素F1α显著增加、LTB4降低以及淋巴细胞显著减少有关。此外，CSE前用布洛芬预处理与一半兔的严重肺损伤有关。肺损伤的严重程度可能与肺泡巨噬细胞数量减少和肺PGI2阻断的联合作用有关。
