侵袭性真菌感染是免疫功能低下人群高死亡率的主要原因，尤其是重症监护病房 (ICU) 患者、晚期癌症患者或严重烧伤患者等重症患者。高钠血症还会增加重症患者的死亡率。两性霉素 B (AmB) 是治疗感染的金标准，但对于重症患者，AmB 由于与红细胞膜上的胆固醇相互作用，静脉注射时会引起血液毒性。这导致 AmB 剂量有限并影响感染的治疗。红细胞膜脂中胆固醇分子的比例高达50 mol%，钠离子可以影响AmB与膜脂之间的相互作用。因此，在真菌感染合并高钠血症的重症患者的复杂临床情况下，两性霉素B与红细胞膜的相互作用值得深入研究。在这项工作中，研究了当胆固醇比例为 50% 时，AmB 与二棕榈酰磷脂酰胆碱 (DPPC)/胆固醇混合单层在高钠离子水平存在下的相互作用。结果表明，在高钠离子水平下，AmB 对减少单层面积的作用在 30 mN/m 时稍强。与正常生理浓度下的钠离子水平相比，高钠离子水平显着削弱了AmB降低DPPC/Chol单层弹性模量的作用。钠离子浓度越高，DPPC/Chol/AmB混合单层的分子间力越弱。扫描电子显微镜 (SEM) 和原子力显微镜 (AFM) 观察表明，在高钠离子水平下，AmB 的存在显着降低了 DPPC/Chol 单层的表面粗糙度。 AmB 可能与胆固醇分子结合，并将胆固醇与单层分离，导致富含胆固醇的单层高度降低，单层区域越来越分散。该结果有利于了解高钠离子水平对AmB与富含胆固醇的红细胞膜关系的影响机制，对于了解高钠离子水平下AmB对红细胞的溶血毒性具有重要价值。版权所有 © 2024 王强李王。

Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50 mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer's area at a high level of sodium ions is slightly stronger at 30 mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.Copyright © 2024 Wang, Qiang, Li and Wang.