Department of Research, Mount Sinai Medical Center, Miami Beach, Florida, United States of America.
Department of Medicine, Mount Sinai Medical Center, Miami Beach, Florida, United States of America.
PLoS One. 2019 Nov 7;14(11):e0224764. doi: 10.1371/journal.pone.0224764. eCollection 2019.
The purpose of this investigation was to ascertain whether nitric oxide (NO) released into the circulation by a noninvasive technology called whole body periodic acceleration (WBPA) could increase mucociliary clearance (MCC). It was based on observations by others that nitric oxide donor drugs increase ciliary beat frequency of nasal epithelium without increasing mucociliary clearance. Tracheal mucous velocity (TMV), a reflection of MCC, was measured in sheep after 1-hour treatment of WBPA and repeated after pretreatment with the NO synthase inhibitor, L-NAME to demonstrated action of NO. Aerosolized human neutrophil elastase (HNE) was administered to sheep to suppress TMV as might occur in cystic fibrosis and other inflammatory lung diseases. WBPA increased TMV to a peak of 136% of baseline 1h after intervention, an effect blocked by L-NAME. HNE reduced TMV to 55% of baseline but slowing was reversed by WBPA, protection lost in the presence of L-NAME. NO released into the circulation from eNOS by WBPA can acutely access airway epithelium for improving MCC slowed in cystic fibrosis and other inflammatory lung diseases as a means of enhancing host defense against pathogens.
本研究旨在确定全身周期性加速（WBPA）这一非侵入性技术所释放到循环系统中的一氧化氮（NO）是否能增加黏液纤毛清除率（MCC）。这是基于其他人的观察结果，即一氧化氮供体药物可以增加鼻上皮的纤毛摆动频率，而不会增加黏液纤毛清除率。在经过 1 小时的 WBPA 处理后，测量绵羊的气管黏液速度（TMV），这是 MCC 的反映，然后在预先用一氧化氮合酶抑制剂 L-NAME 处理后再次测量，以证明 NO 的作用。向绵羊中给予人中性粒细胞弹性蛋白酶（HNE）气溶胶以抑制 TMV，这可能发生在囊性纤维化和其他炎症性肺疾病中。WBPA 将 TMV 增加到干预后 1 小时的基线的 136%，这一作用被 L-NAME 阻断。HNE 将 TMV 降低到基线的 55%，但 WBPA 可逆转这种减速，而 L-NAME 的存在则会使保护作用丧失。NO 通过 WBPA 从 eNOS 释放到循环系统中，可以迅速到达气道上皮，从而改善在囊性纤维化和其他炎症性肺疾病中减缓的 MCC，作为增强宿主防御病原体的一种手段。
