新型解黏液n -乙酰半胱氨酸l-赖氨酸与n -乙酰半胱氨酸的比较:犬气道上皮功能和黏液的变化

R.P. Tomkiewicz , E.M. App , G.T. De Sanctis , M. Coffiner , P. Maes , B.K. Rubin , M. King
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引用次数: 42

摘要

研究了一种新合成的黏液溶解剂n -乙酰半胱氨酸l-赖氨酸(Nacystelyn)。研究了6只健康杂种狗在服用安慰剂、纳斯特琳(NAL)和乙酰半胱氨酸(NAC)计量吸入器(MDI)气溶胶后,气管粘液流速(TMV)、跨上皮电位差(PD)、流变学特性和收集的气道分泌物离子含量。虽然两种处理后TMV均增加,粘弹性降低,但NAL的治疗效果明显更好。此外,NAL增加了气管分泌物的负PD和Cl -含量,NAC后没有观察到这种作用。这两种化合物都增加了青蛙上颚的纤毛搏动频率(CBF),其浓度范围与狗气道近似。由于这两种化合物都能破坏黏液聚合物中的二硫键,所以NAL后黏液流变学和清除率的较大变化,而含水量没有变化,这可以用Cl−含量的增加来解释。Nacystelyn似乎结合了不同的作用模式,协同作用导致气道分泌物清除率的增加。
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A comparison of a new mucolytic N-acetylcysteine l-lysinate with N-acetylcysteine: Airway epithelial function and mucus changes in dog

A newly synthesized mucolytic agent, N-acetylcysteine l-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), tranepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and Cl content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in Cl content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.

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