Cyprus International Institute for Environmental & Public Health, Cyprus University of Technology, Limassol, Cyprus.
Department of Electron Microscopy/Molecular Pathology, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Cyprus School of Molecular Medicine, Nicosia, Cyprus.
Pulm Pharmacol Ther. 2018 Feb;48:15-21. doi: 10.1016/j.pupt.2017.10.010. Epub 2017 Oct 19.
Few studies have examined the potentially therapeutic effect of increasing the production of endogenous nitric oxide (NO) in Primary Ciliary Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In this study we assessed the effect of increasing l-Arginine, as the substrate of NO synthases, on CBF in biopsies of human respiratory ciliated epithelium.
A total of 28 suspect cases with chronic respiratory manifestations referred for PCD diagnostic testing and 8 healthy controls underwent nasal brushing. Obtained epithelial cells were divided between three culture medium 199 solutions, containing different levels of l-Arginine (0.33 mM as baseline, 1 mM and 10 Mm as increased levels). CBF measurements were obtained at 37 °C and 25 °C at 1, 3 and 24 h after sample acquisition.
Among a total of 36 recruited subjects, 8 had PCD confirmed (PCD n = 8), 20 had PCD excluded (non-PCD n = 20) and 8 were healthy controls (Healthy Controls = 8). Among PCD subjects, ciliary motility was characterized by rotational (n = 5) or dyskinetic (n = 3) beating. At 37 °C, compared to baseline, higher levels of l-Arginine resulted in up to 9% CBF increase at 1 h (p = 0.007), up to 9% CBF increase at 3 h (p < 0.001) and up to 12% CBF increase at 24 h (p = 0.002). Similar although smaller scale increases were recorded at 25 °C. The effect of l-Arginine was time dependent (interaction p = 0.002) and was similar in PCD patients, non-PCD chronic respiratory patients and healthy controls (interaction p = 0.800).
l-Arginine increases CBF and merits to be evaluated as a potential stimulator of mucociliary clearance in chronic respiratory conditions and congenital ciliary disorders with residual motility. Larger human studies are needed to confirm these findings.
很少有研究探讨增加内源性一氧化氮（NO）产生对原发性纤毛运动障碍（PCD）和其他慢性呼吸系统疾病的潜在治疗作用。PCD 患者的鼻腔一氧化氮水平较低，并且已经发现与纤毛摆动频率（CBF）受损有关。在这项研究中，我们评估了增加 L-精氨酸（NO 合酶的底物）对人呼吸道纤毛上皮活检组织中 CBF 的影响。
共 28 例有慢性呼吸道表现的疑似病例接受 PCD 诊断检测，8 例健康对照者接受鼻刷。获得的上皮细胞分为三种 199 培养液，含有不同水平的 L-精氨酸（以 0.33mM 为基础水平，1mM 和 10mM 为增加水平）。在样本采集后 1、3 和 24 小时，在 37°C 和 25°C 下测量 CBF。
在总共招募的 36 名受试者中，8 名被确诊为 PCD（PCD 组 n=8），20 名被排除 PCD（非 PCD 组 n=20），8 名是健康对照者（健康对照组 n=8）。在 PCD 患者中，纤毛运动表现为旋转（n=5）或运动障碍（n=3）。在 37°C 下，与基础水平相比，较高水平的 L-精氨酸在 1 小时时导致 CBF 增加 9%（p=0.007），在 3 小时时导致 CBF 增加 9%（p<0.001），在 24 小时时导致 CBF 增加 12%（p=0.002）。在 25°C 下记录到了类似但规模较小的增加。L-精氨酸的作用具有时间依赖性（交互作用 p=0.002），并且在 PCD 患者、非 PCD 慢性呼吸道患者和健康对照者中相似（交互作用 p=0.800）。
L-精氨酸增加了 CBF，值得作为慢性呼吸道疾病和有残余运动能力的先天性纤毛运动障碍的潜在黏液清除刺激物进行评估。需要更大规模的人体研究来证实这些发现。
