中国畜牧兽医

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甘草次酸联合抗结核药对结核杆菌活性研究

邢立群,贾芳   

  1. (河套学院,内蒙古巴彦淖尔 015000)
  • 收稿日期:2014-01-13 出版日期:2014-04-20 发布日期:2014-05-27
  • 通讯作者: 贾芳(1980—),女,硕士,研究方向:微生物与基因工程。Tel: 0478-8418035;E-mail: jiafang198011@163.com
  • 作者简介:邢立群(1976—),女,内蒙古人,学士,研究方向:生物化学。
  • 基金资助:

    内蒙古自治区高等学校科学研究项目(2013NJZY3383)。

Synergistic Effects of 18β-glycyrrhetinic Acid in Combination with Antimycobacterial Drugs against Mycobacterium bovis

XING Li-qun, JIA Fang   

  1. (Hetao College, Bayannur 015000, China)
  • Received:2014-01-13 Online:2014-04-20 Published:2014-05-27

摘要: 研究选取中药单体18β-甘草次酸联合一线抗结核药物异烟肼(INH)、利福平(RFP)和链霉素(SM),利用MABA法检测其体外单独及联合作用于牛源结核分枝杆菌的抗菌活性。18β-甘草次酸单独作用于结核分枝杆菌标准株(ATCC 27294)和牛分枝杆菌标准株(ATCC 19210)的最低抑菌浓度(MIC)分别为50和100 μg/mL。临床分离的2株敏感株和6株耐药株的MIC值分别为25~50和100~200 μg/mL。18β-甘草次酸联合INH、RFP和SM作用于6株耐药株均具有协同作用,且MIC值明显下降,INH的MIC值下降2~32倍(FICIs 0.125~0.375),RFP的MIC值下降4~8倍(FICIs 0.240~0.490),SM的MIC值下降4~16倍(FICIs 0.165~0.460)。中药单体药物对正常细胞BHK-21具有较低的细胞毒性,对肝癌细胞SMMC具有较好抑制作用。结果表明,18β-甘草次酸与抗结核药物INH、RFP和SM联合使用对结核分枝杆菌具有较好的抗菌药理活性。

关键词: 18β -甘草次酸; 抗结核药物; 结核分枝杆菌; 最低抑菌浓度(MIC)

Abstract: In this study,we found that 18β-glycyrrhetinic acid had potent antimycobacterial properties against the drug-susceptible and drug-resistant Mycobacterium bovis. Minimum inhibitory concentration (MIC) were 50 and 100 μg/mL after appling 18β-glycyrrhetinic acid alone aginst ATCC 27294 and ATCC 19210; MICs were 25~50 and 100~200 μg/mL after appling 18β-glycyrrhetinic acid alone aginst 2 drug-susceptible and drug-resistant Mycobacterium bovis. More importantly, they exhibited synergistic effects with the first-line drugs isoniazid (INH), rifampicin (RIF) andstreptomycin (SM) against clinical Mycobacterium bovis isolates, including drug-resistant strains. In combination with asubinhibitory concentration of 18β-glycyrrhetinic acid, the minimum inhibitory concentrations (MICs) of the antituberculosisagents decreased, ranging from 2 to 32, 4 to 8 and 4 to 16 fold for INH (fractional inhibitory concentrationindex (FICIs) 0.125~0.375), RIF (FICIs 0.240~0.490) and SM (FICIs 0.165~0.460), 18β-glycyrrhetinic acid had lesser poisonous to BHK-21 cell and could restraint SMMC fission,respectively. These findings indicated that 18β-glycyrrhetinic acid might serve as potential therapeutic compounds for futureantimycobacterial drug development.

Key words: 18β -glycyrrhetinic acid;antimycobacterial agents;Mycobacterium bovis;minimum inhibitory concentration(MIC)