吸入溴化异丙托品对慢性阻塞性肺疾病大鼠模型气道和肺组织M受体的影响

The effect of inhaled ipratropium bromide on airway and lung tissue muscarinic receptors in a rat model of COPD

目的观察吸入溴化异丙托品对大鼠慢性阻塞性肺疾病（ＣＯＰＤ）模型气道和肺组织Ｍ受体的影响及其规律。方法通过长期吸入高浓度ＳＯ２气体的方法建立大鼠ＣＯＰＤ模型４７只，ＣＯＰＤ大鼠在密闭箱内吸入雾化的０．０２５％溴化异丙托品溶液１０ｍｌ（２次／天，２０分钟／次），应用放射配基结合法测定大鼠气道和肺组织Ｍ受体。结果与对照组相比，ＣＯＰＤ大鼠吸入溴化异丙托品５天，气道和肺组织Ｍ受体密度无明显增加，吸入异丙托品３０天，Ｍ受体的密度显著升高（Ｐ＜０．０５），停药６天后，Ｍ受体的密度基本恢复正常。各组平衡离解常数（Ｋｄ）值差异均无显著性。结论长期吸入溴化异丙托品可上调气道毒蕈碱Ｍ受体，但停药后能较快恢复，气道Ｍ受体的上调可能与长期应用异丙托品患者停药后所出现的暂时性的支气管痉挛及肺功能恶化有关。

Objective To observe the effect of inhaled ipratropium bromide on airway and lung tissue muscarinic receptors (MR) in a rat model of chronic obstructive pulmonary disease (COPD). Methods The rat model of COPD was established by chronic exposure with high concentrations of SO 2 gas, COPD rats inhaled aerosolized 0.025% ipratropium bromide solution 10 ml (twice/d, 20 min/time). The MR was determined by radioligand binding studies with 3H QNB as the ligand. Results Compared with that of control, there was a marked increase in MR density on day 30 of treatment with ipratropium but not on day 5. The MR density decreased and close to normal level on the 6th day after cessation of regular therapy with inhaled ipratropium for 30 days. No significant difference was observed in antagonist affinity (Kd) among different time groups of ipratropium therapy. Conclusions Chronic exposure to the anticholinergic agent ipratropium bromide produces an up regulation of airway MR. The airway MR density can recover to normal when treatment stopped. Up regulation of airway MR is associated with transient bronchoconstriction following cesstion of regular ipratropium therapy and lung function deteriorated following long term inhaled ipratropium bromide.