Stengel P W, Bendele A M, Cockerham S L, Silbaugh S A
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
Am Rev Respir Dis. 1993 Jan;147(1):196-201. doi: 10.1164/ajrccm/147.1.196.
We examined the effect of A23187-induced lung injury on airway responses to a variety of bronchoconstrictive aerosols in conscious guinea pigs. Guinea pigs were exposed to aerosolized A23187 or vehicle for 12 min or until labored breathing began. Animals were allowed to recover for 24 h, and then they were challenged with inhaled histamine, leukotriene D4 (LTD4), platelet-activating factor (PAF), or substance P. Eight minutes after start of the bronchoprovocative aerosol, the guinea pigs were killed and excised lung gas volume (ELGV) measurements were used as an index of in vivo airway obstruction. No differences in ELGV dose-response curves to LTD4 were seen in A23187- and vehicle-exposed animals. A23187 exposure produced small increases in both histamine and PAF sensitivity. However, A23187 caused a much more pronounced leftward shift in the dose-response to substance P. Coadministration of the neutral endopeptidase inhibitor, thiorphan, did not reduce the A23187-related airway responses to substance P. Histologic evaluation of A23187-treated lungs revealed peribronchiolar inflammation, bronchiolar epithelial injury, and mild alveolitis. We conclude that A23187 treatment produces differential airway responses to bronchoactive agents, with a preferential sensitization to substance P.
我们研究了A23187诱导的肺损伤对清醒豚鼠气道对多种支气管收缩气雾剂反应的影响。将豚鼠暴露于雾化的A23187或赋形剂中12分钟，或直至出现呼吸困难。让动物恢复24小时，然后用吸入组胺、白三烯D4（LTD4）、血小板活化因子（PAF）或P物质进行激发试验。在支气管激发气雾剂开始8分钟后，处死豚鼠，并将切除肺气体容积（ELGV）测量值用作体内气道阻塞的指标。在暴露于A23187和赋形剂的动物中，未观察到ELGV对LTD4剂量反应曲线的差异。暴露于A23187使组胺和PAF敏感性均略有增加。然而，A23187导致对P物质的剂量反应曲线更明显地向左移动。同时给予中性内肽酶抑制剂硫磷酰胺，并未降低A23187相关的气道对P物质的反应。对经A23187处理的肺进行组织学评估，发现支气管周围炎症、细支气管上皮损伤和轻度肺泡炎。我们得出结论，A23187治疗对支气管活性剂产生不同的气道反应，对P物质有优先致敏作用。
