蜂毒肽Melittin对小鼠红细胞溶血效应及影响机制分析

The Effect of Melittin on Rat Red Blood Cells and Its Mechanism

蜂毒肽Melittin是一种具有高效抗细菌、真菌、肿瘤细胞等多种生物学活性的抗菌肽,然而其溶血活性限制了其发展为高效抗菌抗癌药物的应用.本文深入分析了Melittin对小鼠红细胞的作用机制,探讨影响Melittin溶血活性的细胞机制.结果表明,Melittin可以引起红细胞膜上形成空洞,抑制细胞内ATPase的活性.红细胞膜中糖蛋白或糖脂糖链中的唾液酸参与Melittin的相互作用,介导Melittin的溶血活性.质膜胆固醇也影响Melittin与红细胞膜相互作用,降低溶血活性.研究还发现,外源添加D-葡萄糖和D-蔗糖能显著抑制Melittin的溶血活性.研究结果为降低抗菌肽溶血性以及推动抗菌肽的药物应用提供了重要理论基础.

Melittin is an antibacterial peptide with variety of biologically activities including highly effective against bacteria,fungi and tumor cells. However,its highly hemolysis activity limits the application as antibacterial and anticancer drugs. This paper deeply analyzed the mechanism of action of Melittin to rat red blood cells,especially for cellular mechanisms. The result showed that Melittin induced a pore-forming on erythrocyte membrane,inhibited the activity of intracellular ATPase. Sialic acid moieties of glycoproteins or glycolipids interact with Melittin mediated hemolytic activity of Melittin. Plasma membrane cholesterol may also interact with Melittin and influence hemolytic activity. The study also found that the addition of exogenous D-glucose and D-sucrose could significantly inhibit the hemolytic activity of Melittin.Our data provided an important theoretical basis for reducing the hemolytic activity of antimicrobial peptides and promoting their drug application.