目的 预测和观察穿心莲内酯总磺化物（AS）联合头孢西丁（FOX）对耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）的联合抑制作用。方法 采用网络药理学预测AS联合FOX对MRSA的作用机制；微量稀释法测定AS、FOX对MRSA的最小抑菌浓度；棋盘法测定两药联用对MRSA的分数抑制浓度指数、确定最佳抑菌浓度比；微孔板法检测给药后MRSA的成熟期细菌生物膜（BF）内活菌数的变化。结果 AS联合FOX针对MRSA的共同作用点是MRSA毒力因子Hla和PVL，另外AS也作用于细菌生物被膜相关分子FnbB。AS和FOX对MRSA的MIC分别为50mg?mL-1和32μg?mL-1；最佳抑菌浓度比为25mg?mL-1 AS+4μg?mL-1 FOX，FICI值=0.625，表现为相加作用；FOX（16、8、4μg?mL-1）单独作用后成熟MRSA BF内活菌数无明显抑制，AS（25、12.5mg?mL-1）单独或联合FOX（16、8、4μg?mL-1）作用后成熟MRSA BF内活菌数均减少（P<0.01）。结论 AS联合FOX干预MRSA有增效作用，与抑制MRSA BF有关，AS与抗生素联用是治疗MRSA感染的潜在有效方案。
OBJECTIVE To predict and observe the synergistic inhibitory effect of andrographolide total sulfonate (AS) with cefoxitin (FOX) on methicillin-resistant Staphylococcus aureus (MRSA).METHODS The effect mechanism of AS with FOX on MRSA was predicted by network pharmacology technique. The minimum inhibitory concentration (MIC) of AS and FOX on MRSA was determined by broth dilution method. The chessboard method was used to determine the fractional inhibition concentration index (FICI) of MRSA and the optimal inhibitory concentration ratio. MRSA was cultured on 96-well plates and the effects of AS and FOX on mature biofilm (BF) were studied using an XTT reduction assay. Changes in the amount of living bacteria were determined with a microplate reader 24h after treatment.RESULTS The common targets of AS with FOX against MRSA were MRSA virulence factors Hla and PVL. AS also acted on bacterial biofilm-related molecule FnbB. The MICs of AS and FOX for MRSA were 50 mg/mL and 32 μg/mL, respectively. The optimal inhibitory concentration ratio was 25 mg/mL AS+4 μg/mL FOX, FICI value=0.625, which showed additive effect. The number of viable bacteria in mature MRSA BF was not inhibited by FOX (16, 8, 4 ug/mL), but decreased by AS (25, 12.5 mg/mL) alone or combined with FOX (16, 8, 4 ug/mL).CONCLUSION AS with FOX has the synergistic effect on MRSA, which is related to inhibiting MRSA BF. AS combined with antibiotics might be a potential effective treatment for MRSA infection.