目的 考察地榆皂苷Ⅱ对耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）的体外抑菌活性以及抑菌机制。方法 肉汤稀释法检测地榆皂苷Ⅱ对16株MRSA的体外抑菌活性；比浊法和菌落计数绘制地榆皂苷Ⅱ对MRSA的生长曲线、杀菌曲线；通过DNA外泄实验，分析地榆皂苷Ⅱ对MRSA细胞壁膜通透性的影响；通过DAPI染色后的荧光强度分析，考察地榆皂苷Ⅱ对MRSA DNA和RNA的影响。结果 地榆皂苷Ⅱ对16株MRSA的最小抑菌浓度（MIC）范围为128～256 μg·mL^-1，最小杀菌浓度（MBC）范围为2～8 mg·mL^-1。生长曲线结果显示，地榆皂苷Ⅱ质量浓度为1×MIC （256 μg·mL^-1）及以上时，生长抑制作用明显；杀菌曲线结果显示，地榆皂苷Ⅱ 2×MIC、4×MIC作用1 h后对MRSA的抑制作用明显，8×MIC、16×MIC分别作用1、2 h后对MRSA起到了完全抑制的作用。2×MIC的地榆皂苷Ⅱ作用于MRSA后，胞外核酸大分子含量显著高于对照组，6 h后核酸外泄量较对照组高26.23%（P＜0.05）。地榆皂苷Ⅱ作用于MRSA菌体后，MRSA DNA和RNA水平明显低于对照组（P＜0.01、0.001）。结论 地榆皂苷Ⅱ对MRSA有良好的抑菌活性，可以通过抑制细菌核酸合成进而抑制MRSA的生长。

Objective To investigate the in vitro antibacterial activity and mechanism of traditional Chinese medicine monomer ziyuglycoside Ⅱ against methicillin-resistant Staphylococcus aureus (MRSA). Method The broth dilution method was used to detect the in vitro antibacterial activity of ziyuglycoside Ⅱ against 16 MRSA strains. Draw the growth curve and bactericidal curve of ziyuglycoside Ⅱ on MRSA using turbidimetry and colony counting. Analyze the effect of ziyuglycoside Ⅱ on the permeability of MRSA cell wall membrane through DNA leakage experiments. By analyzing the fluorescence intensity after DAPI staining, the effect of ziyuglycoside Ⅱ on MRSA DNA and RNA was investigated. Result The minimum inhibitory concentration range of ziyuglycoside Ⅱ on 16 MRSA strains was 128—256 μg·mL^-1, with a minimum bactericidal concentration range of 2—8 mg·mL^-1. The growth curve results showed that when the mass concentration of ziyuglycoside Ⅱ was 1 × MIC (256 μg·mL^-1) and above, the growth inhibition effect was significant. The sterilization curve results show that after one hour of 2 × MIC and 4 × MIC action, the inhibitory effect on MRSA was significant. Ziyuglycoside Ⅱ of 8 × MIC, 16 × MIC completely inhibited MRSA after 1 and 2 hours of action, respectively. After MIC induced action on MRSA, the content of extracellular nucleic acid macromolecules was significantly higher than that of the control group. After six hours, the amount of nucleic acid leakage was 26.23% higher than that of the control group (P＜0.05). After the action of ziyuglycoside Ⅱ on MRSA cells, the levels of MRSA DNA and RNA were significantly lower than those of the control group (P＜0.01, 0.001). Conclusion Ziyuglycoside Ⅱ is an antibacterial drug with good antibacterial activity against MRSA, which can inhibit the growth of MRSA by inhibiting bacterial nucleic acid synthesis.

R285.5

广东省基础与应用基础研究基金项目（2019A1515110092）