Lai Y L, Thacker A, Gairola C G
Division of Pharmacology and Experimental Therapeutics, University of Kentucky College of Pharmacy, Lexington 40536.
J Appl Physiol (1985). 1994 Oct;77(4):1868-74. doi: 10.1152/jappl.1994.77.4.1868.
We established a guinea pig model to investigate effects of in utero and neonatal exposure to sidestream cigarette smoke (SSCS) on bronchial reactivity during early life. Animals were divided into four groups: 1) room air/room air, 2) sham/sham, 3) SSCS/room air, and 4) SSCS/SSCS. Pregnant and neonatal animals of group 1 breathed room air and those of group 2 were sham treated. Pregnant animals of both groups 3 and 4 as well as neonates of group 4 were exposed to SSCS. SSCS exposure was limited to between days 28 and 55 of pregnancy and days 8 and 24 of the neonatal period. Bronchial response to acetylcholine (ACh) and substance P (SP) were determined in very young animals at 25 days of age. Maximal expiratory flow was used as an index of airway dimension. SP, but not ACh, induced a significantly larger decrease in peak maximal expiratory flow in group 4, indicating an important role of neonatal SSCS exposure in augmenting bronchial response to SP. To further investigate the role of tachykinins in cigarette smoke-induced changes in bronchial reactivity, four additional groups (the same as above) of neonates were pretreated with capsaicin to deplete tachykinins. In the SSCS/SSCS group, SP-induced airway hyperreactivity was abolished by capsaicin pretreatment. Furthermore, in all four groups, capsaicin pretreatment abolished the bronchial response to SP but not the response to ACh. In additional very young animals, acute SSCS caused a nonsignificant increase in bronchial response to SP. These results indicate that chronic neonatal SSCS exposure induces bronchial hyperreactivity to SP; this hyperreactivity is abolished by capsaicin pretreatment.
我们建立了一个豚鼠模型，以研究子宫内和新生儿期暴露于侧流香烟烟雾（SSCS）对生命早期支气管反应性的影响。动物被分为四组：1）室内空气/室内空气，2）假手术/假手术，3）SSCS/室内空气，4）SSCS/SSCS。第1组的怀孕和新生动物呼吸室内空气，第2组的动物接受假手术治疗。第3组和第4组的怀孕动物以及第4组的新生动物暴露于SSCS。SSCS暴露仅限于怀孕第28至55天和新生儿期第8至24天。在25日龄的幼小动物中测定支气管对乙酰胆碱（ACh）和P物质（SP）的反应。最大呼气流量用作气道尺寸的指标。在第4组中，SP而非ACh导致最大呼气流量峰值显著下降，表明新生儿期暴露于SSCS在增强支气管对SP的反应中起重要作用。为了进一步研究速激肽在香烟烟雾诱导的支气管反应性变化中的作用，另外四组（与上述相同）新生儿用辣椒素预处理以耗尽速激肽。在SSCS/SSCS组中，辣椒素预处理消除了SP诱导的气道高反应性。此外，在所有四组中，辣椒素预处理消除了支气管对SP的反应，但未消除对ACh的反应。在另外的幼小动物中，急性SSCS导致支气管对SP的反应无显著增加。这些结果表明，新生儿期长期暴露于SSCS会诱导支气管对SP的高反应性；这种高反应性可被辣椒素预处理消除。
