Wang Juan, Qiang Jiahao, Li Jinzi, Wang Dengwu
Xi'an Key Laboratory of Advanced Photo-electronics Materials and Energy Conversion Device, School of Electronic Information, Xijing University, Xi'an, China.
Shaanxi Engineering Research Center of Controllable Neutron Source, School of Electronic Information, Xijing University, Xi'an, China.
Front Mol Biosci. 2024 May 9;11:1405383. doi: 10.3389/fmolb.2024.1405383. eCollection 2024.
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.
侵袭性真菌感染是免疫功能低下人群，尤其是重症患者，如重症监护病房（ICU）患者、晚期癌症患者或严重烧伤患者高死亡率的主要原因。高钠血症也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，但在重症患者中，静脉注射AmB时，由于其与红细胞膜上的胆固醇相互作用，会导致血液毒性。这导致AmB剂量受限，并影响感染的治疗。红细胞膜脂质中胆固醇分子的比例高达50摩尔%，钠离子可影响AmB与膜上脂质的相互作用。因此，在重症真菌感染合并高钠血症的复杂临床情况下，两性霉素B与红细胞膜之间的相互作用值得深入研究。在这项工作中，研究了在胆固醇比例为50%且钠离子水平较高的情况下，AmB与二棕榈酰磷脂酰胆碱（DPPC）/胆固醇混合单分子层之间的相互作用。结果表明，在30 mN/m时，高钠离子水平下AmB对单分子层面积减小的影响略强。与正常生理浓度的钠离子水平相比，高钠离子水平显著削弱了AmB对DPPC/胆固醇单分子层弹性模量的降低作用。钠离子浓度越高，DPPC/胆固醇/AmB混合单分子层的分子间力越弱。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的存在显著降低了DPPC/胆固醇单分子层的表面粗糙度。AmB可能与胆固醇分子结合，并将胆固醇从单分子层中分离出来，导致富含胆固醇的单分子层高度降低，单分子层区域越来越分散。这些结果有助于理解高钠离子水平对AmB与富含胆固醇的红细胞膜之间关系的影响机制，对于理解高钠离子水平下AmB对红细胞的溶血毒性具有重要价值。
