Li A, Seipelt H, Müller C, Shi Y, Artmann M
Department of Cell Biophysics, University of Applied Sciences Aachen, Germany.
Pharmacol Toxicol. 1999 Nov;85(5):206-11. doi: 10.1111/j.1600-0773.1999.tb02010.x.
Salicylamide, sodium salicylate and acetylsalicylic acid are salicylic acid derivates. They differ in their substitution on the benzene ring and may have different effects on membranes. Red blood cells were used as a prototypical cellular system regarding drug mediated plasma bilayer effects. Established photometric methods sensing tiny changes of red blood cell morphology at rest (red blood cell shape) and at very low shear forces (red blood cell stiffness, red blood cell relaxation time) were applied. The derivative induced effects were detected in a time- and dose-dependent manner. Salicylamide induced a most pronounced echinocytic shape at 5 mM. The shape effect was smaller above as well as below 5 mM. Sodium salicylate induced echinocytes with increasing concentrations showing a saturation above 10 mM. In contrast, the shape was not affected by acetylsalicylic acid. All shape changes occurred within 2 min, and were reversible. The above tendencies were in parallel to a slight red blood cell stiffening. The relaxation time continuously increased with increasing concentrations in both salicylamide and sodium salicylate, with salicylamide always acting stronger. Acetylsalicylic acid again showed no effect. We hypothesize that the observed effects of sodium salicylate and salicylamide are due to their phenolic character mediating a molecular hydrophobicity. According to the bilayer couple hypothesis this would lead to an insertion into the red blood cells outer plasma bilayer leaflet. The extension induced here would cause a positive membrane bending leading to echinocytic shapes and the observed loss of red blood cell fluidity. In contrast, the hydrophilic aspirin would penetrate and thus not affect the red blood cell plasma membrane.
水杨酰胺、水杨酸钠和乙酰水杨酸都是水杨酸衍生物。它们在苯环上的取代情况不同，对细胞膜可能有不同的影响。红细胞被用作研究药物介导的血浆双层效应的典型细胞系统。应用已建立的光度法来检测红细胞在静止状态下（红细胞形状）以及在极低剪切力下（红细胞硬度、红细胞弛豫时间）的微小形态变化。衍生物诱导的效应呈时间和剂量依赖性。在5 mM时，水杨酰胺诱导出最明显的棘形红细胞形态。在5 mM以上和以下，形状效应较小。水杨酸钠随着浓度增加诱导出棘形红细胞，在10 mM以上显示出饱和。相比之下，乙酰水杨酸对形状没有影响。所有形状变化都在2分钟内发生，并且是可逆的。上述趋势与红细胞轻微变硬平行。在水杨酰胺和水杨酸钠中，弛豫时间随着浓度增加而持续增加，水杨酰胺的作用总是更强。乙酰水杨酸再次显示无作用。我们假设观察到的水杨酸钠和水杨酰胺的效应是由于它们的酚类性质介导了分子疏水性。根据双层偶联假说，这将导致插入红细胞外血浆双层小叶。此处诱导的伸展将导致正的膜弯曲，从而导致棘形红细胞形状和观察到的红细胞流动性丧失。相比之下，亲水性的阿司匹林会渗透，因此不会影响红细胞质膜。
