Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Auton Neurosci. 2010 Apr 19;154(1-2):74-8. doi: 10.1016/j.autneu.2009.12.002. Epub 2010 Jan 3.
We conducted several experiments that focused on the effect of vagal control on mucociliary clearance (MCC) in murine lungs. We hypothesized that loss of vagal control by chronic denervation (i.e. vagotomy) would reduce both basal MCC and the increase in MCC typically observed upon stimulation of capsaicin sensitive C-fibers. Vagotomy was performed on the right side of C57BL/6 mice and MCC was measured 5 days later. Mucociliary clearance was measured by gamma scintigraphy after oropharyngeal aspiration of the radioisotope (99m)technetium and was expressed as the amount of radioactivity removed from the right lung 6h later. Baseline MCC was unaffected by vagotomy, averaging 6.5+/-4.9% and 6.8+/-5.8%, in 6 vagotomized and 6 non-vagotomized mice (controls), respectively. Mucociliary clearance increased significantly to 12.7+/-5.9% in 9 non-vagotomized mice treated with 1.6 x 10(-9) M capsaicin, a vagally-mediated, nociceptor stimulus (p=0.041). Capsaicin was admixed with (99m)technetium and administered by oropharyngeal aspiration. In contrast, MCC was unchanged from control values in 9 vagotomized, capsaicin-treated animals, averaging 6.0+/-5.5% (p=0.024). These findings suggest that loss of vagal control through denervation does not affect basal MCC in C57BL/6 mice, but does appear to reduce the capacity of mice to respond to nociceptor agents that stimulate MCC. These data could have implications for patients whose lungs are denervated due to lung transplantation, since they may be at risk for an inadequate MCC response to inhaled irritants and inflammatory mediators, which are also nociceptor stimuli.
我们进行了几项实验，重点研究迷走神经控制对小鼠肺部黏液纤毛清除（MCC）的影响。我们假设慢性去神经支配（即迷走神经切断术）会降低基础 MCC 和通常在辣椒素敏感 C 纤维刺激时观察到的 MCC 增加。在 C57BL/6 小鼠的右侧进行迷走神经切断术，并在 5 天后测量 MCC。通过放射性同位素（99m）锝的口咽吸入后进行闪烁照相术测量黏液纤毛清除率，并表示 6 小时后从右肺去除的放射性活度量。基线 MCC 不受迷走神经切断术影响，在 6 只迷走神经切断术和 6 只非迷走神经切断术（对照）小鼠中，平均值分别为 6.5+/-4.9%和 6.8+/-5.8%。在 9 只未接受迷走神经切断术的小鼠中，用 1.6 x 10(-9) M 辣椒素处理后，MCC 显著增加至 12.7+/-5.9%，这是一种迷走神经介导的伤害感受器刺激（p=0.041）。将辣椒素与（99m）锝混合并通过口咽吸入给予。相比之下，在 9 只接受迷走神经切断术和辣椒素治疗的动物中，MCC 与对照值相比无变化，平均值为 6.0+/-5.5%（p=0.024）。这些发现表明，通过去神经支配丧失迷走神经控制不会影响 C57BL/6 小鼠的基础 MCC，但似乎会降低小鼠对刺激 MCC 的伤害感受器剂的反应能力。这些数据可能对由于肺移植而导致肺部去神经支配的患者具有重要意义，因为他们可能面临吸入性刺激物和炎症介质的 MCC 反应不足的风险，这些介质也是伤害感受器刺激物。
