Granström Bengt W, Xu Cang-Bao, Nilsson Elisabeth, Vikman Petter, Edvinsson Lars
Department of Medicine, Clinical sciences, Lund University, Lund, Sweden.
BMC Pulm Med. 2006 Mar 15;6:6. doi: 10.1186/1471-2466-6-6.
Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively.
Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors) and endothelin-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies.
After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism.
The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.
众所周知，吸烟会导致支气管发生慢性炎症变化，并促使气道高反应性，如在支气管哮喘中所见。为研究吸烟对大鼠气道内皮素系统的影响，分别将支气管段暴露于香烟烟雾中的二甲基亚砜可溶性吸烟颗粒（DSP）、尼古丁和二甲基亚砜中。
将分离的大鼠支气管段在单独存在或不存在DSP、尼古丁或二甲基亚砜的情况下培养24小时。通过使用灵敏的肌动描记器研究对沙拉毒素6c（ETB受体的选择性激动剂）和内皮素-1（ETA和ETB受体激动剂）的收缩反应。在引入ET-1之前，使用S6c使ETB受体脱敏。观察到的剩余收缩性被认为是ETA受体选择性激活的结果。使用实时定量PCR分析ETA和ETB受体mRNA表达。在用选择性抗体过夜孵育后，通过免疫组织化学结合共聚焦显微镜研究ETA和ETB受体的定位和浓度。
与DSP一起培养24小时后，支气管段显示出由ETA和ETB受体介导的收缩性增加，而与尼古丁一起培养则不影响其收缩性。其收缩性的上调被翻译抑制剂环己酰亚胺处理所减弱。单独暴露于二甲基亚砜或尼古丁暴露后，ETA和ETB受体mRNA的表达没有显著变化，尽管免疫组织化学显示在存在DSP的情况下孵育后平滑肌中ETA和ETB受体明显增加。总体而言，这被视为存在一种翻译机制。
大鼠支气管暴露于DSP时收缩性增加似乎是由于一种翻译机制。
