Brajtburg J, Medoff G, Kobayashi G S, Elberg S, Finegold C
Antimicrob Agents Chemother. 1980 Oct;18(4):586-92. doi: 10.1128/AAC.18.4.586.
The effects of large polyenes (heptaenes and the "degenerate heptaene" nystatin) on human erythrocytes were found to occur in three separate stages. Stage I was a reversible increase in cell membrane permeability to monovalent cations and occurred at low antibiotic concentrations. At intermediate antibiotic concentrations, an irreversible increase in cell membrane permeability to cations (stage II) occurred, which then led to swelling of cells and hemolysis (stage III). Hemolysis could be prevented by sucrose, mannitol, or melezitose, but stages I and II still occurred under these conditions. The effects of the small polyenes (pentaenes and a tetraene) occurred in only one stage. Changes in cell membrane permeability (stages I and II) were not noted before hemolysis (stage III) even in the presence of carbohydrate. Carbohydrates gave only weak, transient protection from the hemolytic action of small polyenes, probably because the membrane damage induced by these antibiotics was more extensive than that induced by the large polyenes. In the presence of sucrose, large polyenes were able to inhibit the hemolytic action of small polyenes, implying that both antibiotics have the same binding sites.
发现大的多烯类（七烯类和“退化七烯”制霉菌素）对人红细胞的作用分三个不同阶段出现。第一阶段是细胞膜对单价阳离子的通透性可逆性增加，发生在低抗生素浓度时。在中等抗生素浓度下，细胞膜对阳离子的通透性出现不可逆增加（第二阶段），随后导致细胞肿胀和溶血（第三阶段）。蔗糖、甘露醇或松三糖可防止溶血，但在这些条件下第一阶段和第二阶段仍会发生。小的多烯类（五烯类和一种四烯类）的作用仅在一个阶段出现。即使存在碳水化合物，在溶血（第三阶段）之前也未观察到细胞膜通透性的变化（第一阶段和第二阶段）。碳水化合物对小多烯类的溶血作用仅提供微弱、短暂的保护，可能是因为这些抗生素诱导的膜损伤比大的多烯类更广泛。在蔗糖存在的情况下，大的多烯类能够抑制小多烯类的溶血作用，这意味着两种抗生素具有相同的结合位点。
