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[不同α-拟交感神经药物和苯扎氯铵对体外培养的人鼻黏膜细胞纤毛摆动频率的影响]

[The influence of different alpha-sympathomimetic drugs and benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells].

作者信息

Mickenhagen A, Siefer O, Neugebauer P, Stennert E

机构信息

Jean-Uhrmacher-Institut, Universität zu Köln, Köln.

出版信息

Laryngorhinootologie. 2008 Jan;87(1):30-8. doi: 10.1055/s-2007-966891. Epub 2007 Sep 18.

Abstract

BACKGROUND

An appropriate in-vitro model of the human nasal mucosa was developed, which allowed to measure the influence of different pharmaceutical substances on the ciliary beat frequency (CBF) under standardized conditions.

METHOD

The present study describes the effect of the alpha-sympathomimetic drugs naphazolin, xylometazolin and oxymetazolin as pure substances and the preservative Benzalkonium chloride in rising concentrations on the CBF. For these investigations human cells of the human nasal mucosa were cultured, which exhibited a high constancy during the equilibration measurements over at least 200 minutes.

RESULTS

The alpha-sympathomimetic drugs oxymetazoline in the concentration of 0.01% and 0.001% as well as naphazoline within all three concentrations did not show any change of the CBF. Whereas xylometazoline in the concentration of 0.1% caused a high-significant decrease of the CBF. This decrease of the CBF was however partially reversible after rinsing out. Oxymetazolin showed likewise a significant decrease of the CBF in the concentration of 0.1%. This effect however was not reversible after rinsing out with substrate-free medium, but on the contrary showed up a further decrease of CBF. The preservative benzalkonium chloride effected an irreversible ciliostatic activity already in the concentration of 0.005%.

CONCLUSIONS

From the three investigated alpha-sympathomimetic drugs only naphazoline in all measured concentrations did not show any toxic effect. With regard to its therapeutic application this drug in the concentrations 0.001%-0.1% should be preferred to all other alpha-sympathomimetic drugs. Oxymetazoline in the concentration of 0.01% and 0.001% had no toxic effect as well. It however caused an irreversible damage to the cilia in the concentration of 0.1%. This should be considered for the application of rhinological drugs especially in children. The same attention is demanded for xylometazoline, causing a high significant release of CBF in the concentration of 0.1%, which is only partially reversible. Due to the results of this study it has strongly to be advised against the use of all rhinological drugs containing the preservative benzalkonium chloride.

摘要

背景

建立了一种合适的人鼻黏膜体外模型,该模型能够在标准化条件下测量不同药物对纤毛摆动频率(CBF)的影响。

方法

本研究描述了α-拟交感神经药萘甲唑啉、赛洛唑啉和羟甲唑啉作为纯物质以及防腐剂苯扎氯铵浓度升高时对CBF的影响。为进行这些研究,培养了人鼻黏膜的人类细胞,这些细胞在至少200分钟的平衡测量期间表现出高度稳定性。

结果

浓度为0.01%和0.001%的α-拟交感神经药羟甲唑啉以及所有三种浓度的萘甲唑啉均未显示CBF有任何变化。而浓度为0.1%的赛洛唑啉导致CBF显著降低。不过,冲洗后这种CBF降低部分可逆。羟甲唑啉在浓度为0.1%时同样显示CBF显著降低。然而,用无底物培养基冲洗后这种效应不可逆,相反CBF进一步降低。防腐剂苯扎氯铵在浓度为0.005%时就产生了不可逆的抑纤毛活性。

结论

在所研究的三种α-拟交感神经药中,只有所有测量浓度的萘甲唑啉未显示任何毒性作用。就其治疗应用而言,浓度为0.001% - 0.1%的该药物应优于所有其他α-拟交感神经药。浓度为0.01%和0.001%的羟甲唑啉也没有毒性作用。然而,其在浓度为0.1%时对纤毛造成了不可逆损伤。在应用鼻科药物时,尤其是儿童用药时应考虑到这一点。赛洛唑啉也需要同样关注,其在浓度为0.1%时导致CBF显著降低,且只是部分可逆。基于本研究结果,强烈建议不要使用所有含有防腐剂苯扎氯铵的鼻科药物。

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