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钙通道阻滞剂、钙调蛋白拮抗剂及氧自由基清除剂对红细胞膜的稳定作用

Erythrocyte membrane stabilization by calcium channel blockers, calmodulin antagonists and scavengers of oxygen free radicals.

作者信息

Beresewicz A, Karwatowska-Prokopczuk E

机构信息

Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warszawa, Poland.

出版信息

Pol J Pharmacol Pharm. 1990 Jul-Aug;42(4):355-64.

PMID:2097597
Abstract

Calcium channel blockers (nifedipine, verapamil, diltiazem), calmodulin antagonists (trifluoperazine, calmidazolium, compound 48/80) and anti-free radical agents (allopurinol, desferrioxamine, mannitol, L-methionine) were tested for their potency to stabilize human erythrocytes against hypotonic hemolysis. The anti-free radical agents and compound 48/80 did not confer the membrane stabilization. Nifedipine, verapamil, diltiazem, calmidazolium and trifluoperazine at low concentrations, protected the cells from the hypotonic hemolysis while at higher concentrations they caused lysis. Similar biphasic changes were produced by the detergents sodium dodecyl sulphate (SDS) and Triton X-100. The drug concentration-dependency of the biphasic changes in the erythrocytes osmotic fragility produced by calcium channel blockers and calmodulin antagonists was not affected by low concentrations of SDS and Triton X-100. On the other hand, these drugs did not prevent the hemolysis produced by high concentrations of the detergents. The above as well as the observation that the membrane stabilization is conferred only by relatively high concentrations of calcium channel blockers and calmodulin antagonists suggest that membrane stabilization is not responsible for anti-ischemic effects of these agents reported in the literature.

摘要

对钙通道阻滞剂(硝苯地平、维拉帕米、地尔硫䓬)、钙调蛋白拮抗剂(三氟拉嗪、氯咪巴唑、48/80化合物)和抗自由基剂(别嘌呤醇、去铁胺、甘露醇、L-蛋氨酸)进行了测试,以检验它们稳定人红细胞抵抗低渗溶血的能力。抗自由基剂和48/80化合物并未赋予膜稳定性。低浓度的硝苯地平、维拉帕米、地尔硫䓬、氯咪巴唑和三氟拉嗪可保护细胞免受低渗溶血,而高浓度时则会导致细胞裂解。十二烷基硫酸钠(SDS)和 Triton X-100等洗涤剂也产生了类似的双相变化。低浓度的SDS和 Triton X-100不会影响钙通道阻滞剂和钙调蛋白拮抗剂引起的红细胞渗透脆性双相变化的药物浓度依赖性。另一方面,这些药物并不能阻止高浓度洗涤剂引起的溶血。上述情况以及膜稳定性仅由相对高浓度的钙通道阻滞剂和钙调蛋白拮抗剂赋予这一观察结果表明,膜稳定性并非文献中报道的这些药物抗缺血作用的原因。

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