卡泊三醇增强人鼻上皮细胞纤毛摆动幅度。
Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells.
机构信息
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
出版信息
Laryngoscope. 2020 May;130(5):E289-E297. doi: 10.1002/lary.28185. Epub 2019 Jul 11.
OBJECTIVE
Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture.
METHODS
The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera.
RESULTS
CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl concentration ([Cl ] ) in cHNECs. The CCis' actions were mimicked by the Cl -free NO solution. In contrast, prior treatment of NPPB (20 μM) or CFTR(inh)-172 (1 μM), which increased [Cl ] by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 μM) did not inhibit the CCis' actions, although it decreased [Cl ] by 10% and CBD by 15%. Thus, CCis stimulates Cl channels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints.
CONCLUSION
CCis increased CBD by 30% in cHNECs via an [Cl ] decrease stimulated by activation of Cl channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR.
LEVEL OF EVIDENCE
NA. Laryngoscope, 130:E289-E297, 2020.
目的
粘蛋白溶解剂（CCis）是一种黏液活性药物，用于改善鼻-鼻窦疾病的症状。然而，CCis 对鼻纤毛摆动的影响尚不确定。我们在原代培养的人鼻黏膜上皮细胞（cHNECs）中检测 CCis 对纤毛摆动距离（CBD，幅度指标）和纤毛摆动频率（CBF）的影响。
方法
从因慢性鼻窦炎（CS）或变应性鼻炎（AR）而行手术的患者的鼻组织中分离出 cHNECs。使用配备高速摄像机的视频显微镜测量 CBD 和 CBF。
结果
CCis 使 CBD 增加 30%，但不影响 CBF，同时降低 cHNECs 中的细胞内 Cl-浓度([Cl-])。CCis 的作用可被无 Cl-的 NO 溶液模拟。相反，CFTR 抑制剂 CFTR(inh)-172（1μM）或 NPPB（20μM）预处理可使[Cl-]增加 20%，使 CBF 降低 10%，CBD 降低 25%，并抑制 CCis 的作用。然而，CFTR 氯离子通道抑制剂 T16Ainh-A01（10μM）预处理虽然使[Cl-]降低 10%，CBD 降低 15%，但并不抑制 CCis 的作用。因此，CCis 刺激包括 CFTR 在内的氯离子通道。此外，CCis 增强了 cHNECs 中纤毛摆动驱动的微珠转运。CCis 在两种患者来源的 cHNECs 中的作用相似。
结论
CCis 通过激活氯离子通道（包括 CFTR）导致[Cl-]下降，使 CBD 增加 30%。CCis 可能通过增加 CS 或 AR 患者的 CBD 来刺激鼻黏液清除。
证据等级
无。喉镜，130：E289-E297，2020 年。
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