Shore S, Kobzik L, Long N C, Skornik W, Van Staden C J, Boulet L, Rodger I W, Pon D J
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Am J Respir Crit Care Med. 1995 Jun;151(6):1931-8. doi: 10.1164/ajrccm.151.6.7767542.
Chronic exposure of rats to high concentrations of SO2 gas causes pathologic changes in airway similar to those seen in human chronic bronchitis. The purpose of this study was to examine the pulmonary mechanical correlates of these changes and to quantify the extent of mucous hypersecretion by measuring changes in mucous glycoproteins. Female Sprague-Dawley rats were exposed to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 4 wk. Control rats were exposed to air only. On the day after the last SO2 exposure, rats were anesthetized, instrumented for the measurement of pulmonary resistance (RL) and dynamic compliance (Cdyn), and ventilated. Chronic SO2 exposure caused a small but significant increase in RL and decrease in Cdyn. Airway responsiveness to inhaled aerosolized methacholine was increased in SO2-exposed rats, as indicated by approximately 6.6- and 4.6-fold decreases respectively, in the doses of inhaled methacholine required to double RL or decrease Cdyn to 50% of baseline. SO2 exposure had no effect on the contractile response of the trachea measured in vitro. Tracheae and lungs from SO2-exposed animals exhibited 140 and 535% increases in measured neutral mucous glycoproteins, respectively, and 33 and 37% increases in acid glycoproteins. Our results indicate that this animal model of chronic bronchitis mimics the mucous hypersecretion, airway obstruction, and increased airway responsiveness observed in human bronchitis and may allow us to begin to probe their mechanistic basis.
大鼠长期暴露于高浓度二氧化硫气体中会导致气道出现病理变化，类似于人类慢性支气管炎的症状。本研究旨在探讨这些变化的肺力学相关性，并通过测量黏液糖蛋白的变化来量化黏液分泌过多的程度。将雌性斯普拉格-道利大鼠暴露于250 ppm的二氧化硫气体中，每天5小时，每周5天，持续4周。对照大鼠仅暴露于空气中。在最后一次二氧化硫暴露后的第二天，将大鼠麻醉，安装测量肺阻力（RL）和动态顺应性（Cdyn）的仪器，并进行通气。长期暴露于二氧化硫会导致RL略有但显著增加，Cdyn降低。暴露于二氧化硫的大鼠对吸入雾化乙酰甲胆碱的气道反应性增加，这分别表现为使RL加倍或使Cdyn降至基线的50%所需的吸入乙酰甲胆碱剂量分别降低约6.6倍和4.6倍。二氧化硫暴露对体外测量的气管收缩反应没有影响。暴露于二氧化硫的动物的气管和肺中，测得的中性黏液糖蛋白分别增加了140%和535%，酸性糖蛋白分别增加了33%和37%。我们的结果表明，这种慢性支气管炎动物模型模拟了人类支气管炎中观察到的黏液分泌过多、气道阻塞和气道反应性增加的现象，并可能使我们开始探究其机制基础。
