万古糖胺对万古霉素刺激小鼠巨噬细胞RAW 264.7吞噬功能的影响  

Effect of vancoglycosamine on vancomycin-induced phagocytosis in mouse macrophages RAW 264.7

作　　者：陈志红 魏维[1,2] 陈代杰 殷瑜[1,2] CHEN Zhi-hong;WEI Wei;CHEN Dai-jie;YIN Yu(School of Pharmacy,Shanghai Jiaotong University,Shanghai 200240,China;Shanghai Laiyi Biological Research and Development Center,Shanghai 201203,China)

机构地区：[1]上海交通大学药学院,上海200240 [2]上海来益生物研究开发中心,上海201203

出　　处：《中国新药杂志》2020年第9期1040-1044,共5页Chinese Journal of New Drugs

摘　　要：目的:探究万古糖胺对万古霉素刺激小鼠巨噬细胞RAW 264. 7吞噬功能的影响,并初步探索其可能的调控机制。方法:用一定浓度的万古霉素和L-万古糖胺万古霉素LYWW01处理巨噬细胞后,与耐甲氧西林金黄色葡萄球菌共孵育,通过稀释涂布平板计数法测定巨噬细胞内的活菌数。在脂磷壁酸的刺激下,检测巨噬细胞内的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素6(interleukin-6,IL-6)以及ROS水平,初步评价万古糖胺可能的调控机制。结果:20μmol·L^-1 LYWW01处理组的巨噬细胞吞噬活性高于万古霉素处理组,进一步研究发现LYWW01处理巨噬细胞对其吞噬活性的影响呈现浓度依赖性的降低效果。以刺激吞噬功能最强的2μmol·L^-1 LYWW01处理巨噬细胞后,其TNF-α的表达以及ROS的产生均高于同浓度的万古霉素处理组,结果具有统计学差异(P <0. 05)。结论:万古糖胺能增强万古霉素对巨噬细胞吞噬活性的影响,其机制可能是通过ROS依赖性的氧化还原信号调控细胞因子TNF-α的表达。Objective:To examine the effect of vancoglycosamine on vancomycin-induced phagocytosis in mouse macrophages RAW 264.7 in vitro and to initially explore its possible regulatory mechanisms.Methods:Macrophages were treated with vancomycin and L-vancoglycosaminyl vancomycin LYWW01 at a certain concentration,an then co-incubated with methicillin-resistant Staphylococcus aureus(MRSA).The number of viable bacteria in macrophages was determined by dilution coating plate counting method.Furthermore,the levels of cytokines(TNF-αand IL-6)and ROS in macrophages stimulated by lipoteichoic acid were monitored,from which the possible regulatory mechanisms were preliminarily evaluated.Results:The phagocytosis of macrophages in the 20μmol·L^-1 LYWW01 group was significantly higher than that in the vancomycin group(P<0.05).In addition,macrophages in LYWW01 group showed a concentration-dependent reduction in their phagocytosis.Furthermore,after stimulated by LYWW01 at optimum concentration of 2μmol·L^-1,the TNF-αand ROS of macrophages were significantly higher than those in vancomycin group(P<0.05).Conclusion:Vancoglycosamine could enhance the effect of vancomycin on the phagocytosis of macrophages.The mechanism might be the regulation of TNF-αcytokine expression through ROS-dependent redox signaling.

关 键 词：万古霉素 万古糖胺 巨噬细胞 吞噬功能 机制 

分 类 号：R968[医药卫生—药理学]