目的 考察地榆皂苷Ⅱ對耐甲氧西林金黃色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）的體外抑菌活性以及抑菌機制。方法 肉湯稀釋法檢測地榆皂苷Ⅱ對16株MRSA的體外抑菌活性；比濁法和菌落計數繪制地榆皂苷Ⅱ對MRSA的生長曲線、殺菌曲線；通過DNA外泄實驗，分析地榆皂苷Ⅱ對MRSA細胞壁膜通透性的影響；通過DAPI染色后的熒光強度分析，考察地榆皂苷Ⅱ對MRSA DNA和RNA的影響。結果 地榆皂苷Ⅱ對16株MRSA的最小抑菌濃度（MIC）范圍為128～256 μg·mL^-1，最小殺菌濃度（MBC）范圍為2～8 mg·mL^-1。生長曲線結果顯示，地榆皂苷Ⅱ質量濃度為1×MIC （256 μg·mL^-1）及以上時，生長抑制作用明顯；殺菌曲線結果顯示，地榆皂苷Ⅱ 2×MIC、4×MIC作用1 h后對MRSA的抑制作用明顯，8×MIC、16×MIC分別作用1、2 h后對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顯著高于對照組，6 h后核酸外泄量較對照組高26.23%（P＜0.05）。地榆皂苷Ⅱ作用于MRSA菌體后，MRSA DNA和RNA水平明顯低于對照組（P＜0.01、0.001）。結論 地榆皂苷Ⅱ對MRSA有良好的抑菌活性，可以通過抑制細菌核酸合成進而抑制MRSA的生長。

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

廣東省基礎與應用基礎研究基金項目（2019A1515110092）