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黄绵马酸BB对MRSA和MSSA的体内外抗菌作用研究                                                           Δ



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          陈 聪 ,庄素琪 ,江 涛 ,沈志滨 ,陈艳芬 ,司徒莹 ,杨超燕 ,唐春萍 (1.广东药科大学中药学院,
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          广州 510006;2.广东药科大学实验动物中心,广州 510006;3.广州市新药筛选模型系统建设与应用重点实
          验室,广州 510006;4.广东省局部精确给药系统工程中心,广州 510006)
          中图分类号 R965;R285.5         文献标志码 A          文章编号     1001-0408(2022)21-2615-07
          DOI  10.6039/j.issn.1001-0408.2022.21.10
          摘  要 目的 探究黄绵马酸BB对皮肤和软组织感染主要致病菌耐甲氧西林金黄色葡萄球菌(MRSA)和甲氧西林敏感金黄色葡
          萄球菌(MSSA)的体内外抗菌作用。方法 采用微量稀释法测定黄绵马酸 BB 对 10 株 MRSA 和 13 株 MSSA 的最小抑菌浓度
         (MIC)和最小杀菌浓度(MBC),采用平板法绘制MRSA11和MSSA23菌株的时间-杀菌曲线,采用棋盘稀释法测定黄绵马酸BB与
          莫匹罗星的联用抑菌效果;建立小鼠皮肤脓肿模型,评价0.5%、1%、2%黄绵马酸BB乳膏对MRSA11、MSSA23菌株的体内抗菌作
          用;采用扫描电镜观察黄绵马酸BB对MRSA11、MSSA23菌株形态的影响,并检测两种菌株的核酸外渗含量和胞外蛋白含量。结果
          黄绵马酸 BB 对 10 株 MRSA 的 MIC 为 6.30~80.00 μg/mL,MBC 为 40.00~640.00 μg/mL;对 13 株 MSSA 的 MIC 为 40.00~80.00
          μg/mL,MBC为63.50~126.99 μg/mL。黄绵马酸BB干预MRSA11、MSSA23菌株36 h后,杀菌率可达99.9%。黄绵马酸BB与莫
          匹罗星联用对MRSA菌株的作用为相加,对MSSA菌株的作用为相加或协同。0.5%、1%、2%黄绵马酸BB乳膏均能在一定程度上
          减小皮肤脓肿模型小鼠皮肤脓肿体积和降低细菌含量(P<0.05),改善模型小鼠皮肤脓肿部位的炎症病理变化。黄绵马酸BB可
          使MRSA11、MSSA23菌体细胞皱缩、破裂以及核酸外渗含量和胞外蛋白含量显著升高(P<0.01)。结论 黄绵马酸BB对MRSA、
          MSSA均具有良好的体内外抗菌作用,其机制可能与改变细胞膜通透性有关。
          关键词 黄绵马酸BB;皮肤和软组织感染;耐甲氧西林金黄色葡萄球菌;甲氧西林敏感金黄色葡萄球菌;抗菌;皮肤脓肿

          Study on antibacterial effects of flavaspidic acid BB against MRSA and MSSA in vitro and in vivo
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          CHEN Cong ,ZHUANG Suqi ,JIANG Tao ,SHEN Zhibin ,CHEN Yanfen ,SITU Ying ,YANG Chaoyan ,
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          TANG Chunping (1. School of TCM,Guangdong Pharmaceutical University,Guangzhou 510006,China;
          2. Laboratory Animal Center,Guangdong Pharmaceutical University,Guangzhou 510006,China;3. Guangzhou
          Key Laboratory of New Drug Screening Model System Construction and Application,Guangzhou 510006,
          China;4. Guangdong Local Precision Drug Delivery System Engineering Center,Guangzhou 510006,China)
          ABSTRACT   OBJECTIVE To investigate the antibacterial activities of flavaspidic acid BB against the main pathogens of skin
          and soft tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus
          aureus (MSSA) in vitro and in vivo. METHODS Microdilution method was used to determine the minimum inhibitory
          concentration(MIC)and minimum bactericidal concentration(MBC)of flavaspidic acid BB on 10 strains of MRSA and 13 strains
          of MSSA;time-kill curves of MRSA11 and MSSA23 strains were drawn by plate method;the checkerboard dilution method was
          used to determine the combined antibacterial effect of flavaspidic acid BB and mupirocin;the skin abscess model of mice was
          established to evaluate the antibacterial effects of 0.5%,1%,2% flavaspidic acid BB cream on MRSA11 or MSSA23 strains in
          vivo;scanning electron microscopy was used to observe the effects of flavaspidic acid BB on the morphology of MRSA11 or
          MSSA23 strains. The contents of nucleic acid leakage and extracellular protein were also determined. RESULTS MIC and MBC
          ranges of flavaspidic acid BB against 10 strains of MRSA were 6.30-80.00 μg/mL and 40.00-640.00 μg/mL;MIC and MBC ranges
          of 13 strains of MSSA were 40.00-80.00 μg/mL and 63.50-126.99 μg/mL,respectively. The bactericidal rate of MRSA11 and
          MSSA23 strains were 99.9% after interfered with plavaspidic acid BB for 36 h. The combination of flavaspidic acid BB and
          mupirocin showed an additive effect on MRSA strain and an additive or synergistic effect on MSSA strain. The 0.5%,1% and 2%
          flavaspidic acid BB cream could reduce the volume of abscess and the bacterial load of skin abscess model mice to some extent
         (P<0.05),and improved the pathological changes of skin inflammation in skin abscess site of mice. Flavaspidic acid BB could
                                                             make MRSA11 and MSSA23 cells shrinkage and rupture,and
             Δ 基金项目 广东省省级科技计划项目(No.2015B020234009)
                                                             significantly increase the contents of nucleic acid leakage and
             *第一作者 硕士研究生。研究方向:中药药效评价与临床应用。
          E-mail:1045002556@qq.com                           extracellular protein (P<0.01). CONCLUSIONS Flavaspidic
             # 通信作者 教授,硕士生导师。研究方向:中药药效与安全性评                  acid BB shows good antibacterial effect on MRSA and MSSA
          价。E-mail:tchp66@163.com                            in vitro and in vivo,the mechanism of which may be related


          中国药房    2022年第33卷第21期                                            China Pharmacy 2022 Vol. 33 No. 21  ·2615·
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