Stavert D M, Archuleta D C, Holland L M, Lehnert B E
J Toxicol Environ Health. 1986;17(2-3):249-67. doi: 10.1080/15287398609530821.
This study assessed the relationship between nitrogen dioxide inhalation and the development of pulmonary emphysema and investigated how the severity of preexisting emphysema brought about by protease (elastase) instillation into the lung may be augmented by a subchronic exposure to a relatively high concentration of nitrogen dioxide. Lungs of adult Fischer-344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25-d exposure to 35 ppm nitrogen dioxide (NO2), and (3) elastase instillation followed by 25-d exposure to 35 ppm NO2 (E + NO2). Rats instilled with sterile normal saline and subsequently exposed to filtered air served as a control group (NS). Residual volumes (RV) of the NO2 and NS groups were virtually identical, whereas the RV of the E and E + NO2 lungs (2.3 and 2.3 ml, respectively) were significantly greater than those of the NS and NO2 lungs (1.3 and 1.4 ml, respectively). Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO2 groups; NO2 alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO2 exposed lungs were essentially identical with average values of approximately 62 micron. This morphometric parameter was substantially increased in the E- and E + NO2-exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO2 lungs (approximately 95 and approximately 97 micron, respectively). From these data, as well as histologic examinations of lung sections for evidence of emphysema, we conclude that (1) a subchronic, moderately high level of NO2 exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease-induced emphysema or bring about a progression in preexisting emphysema.
本研究评估了吸入二氧化氮与肺气肿发展之间的关系，并研究了通过向肺部注入蛋白酶（弹性蛋白酶）所引发的已有肺气肿的严重程度如何因亚慢性暴露于相对高浓度的二氧化氮而加剧。对成年Fischer - 344大鼠的肺进行评估，观察其在以下情况后的肺气肿变化：（1）单次气管内注入弹性蛋白酶（E）；（2）暴露于35 ppm二氧化氮（NO₂）25天；（3）注入弹性蛋白酶后再暴露于35 ppm NO₂25天（E + NO₂）。注入无菌生理盐水并随后暴露于过滤空气的大鼠作为对照组（NS）。NO₂组和NS组的残气量（RV）实际上相同，而E组和E + NO₂组肺的RV（分别为2.3和2.3 ml）显著大于NS组和NO₂组肺的RV（分别为1.3和1.4 ml）。E组和E + NO₂组在切除肺体积和肺总量方面获得了方向相似的变化；然而，单独的NO₂并未改变这些容积参数。各实验组之间在动脉血气和pH值、分钟通气量或呼吸频率方面未发现差异。NS组和暴露于NO₂的肺所获得的平均线性截距值（MLI）与约62微米的平均值基本相同。在暴露于E和E + NO₂的肺中，这个形态学参数显著增加；然而，E组和E + NO₂组肺的MLI值之间未发现显著差异（分别约为95和约97微米）。根据这些数据以及对肺切片进行的肺气肿证据组织学检查，我们得出结论：（1）在大鼠模型中，亚慢性、中等高水平的NO₂暴露不会产生不可逆的肺气肿病变；（2）在向大鼠肺部注入弹性蛋白酶后，将其暴露于35 ppm的环境中25天，不会增强蛋白酶诱导的肺气肿，也不会使已有的肺气肿病情进展。
