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穿心莲内酯抑制铜绿假单胞菌外排泵MexAB—OprM的作用
  • ISSN号:1001-5213
  • 期刊名称:《中国医院药学杂志》
  • 时间:0
  • 分类:R285.6[医药卫生—中药学;医药卫生—中医学]
  • 作者机构:[1]华中科技大学同济医学院附属同济医院感染科,湖北武汉430030, [2]湖北省中山医院肝病科,湖北武汉430013, [3]温州市中医院肝病科,浙江温州325000, [4]三峡大学第一临床医学院宜昌市中心人民医院,湖北宜昌443003
  • 相关基金:国家自然科学基金资助项目(编号:30571647);湖北省卫生厅科研基金项目(编号:NX200506);国家重点基础研究发展(973计划)(编号:2007CB512900)
中文摘要:

目的:研究穿心莲内酯对铜绿假单胞菌外排泵MexAB-OprM的作用及其机制。方法:采用实时荧光定量PCR分别检测PAO1和MexAB-OprM过度表达株Mex1、Mex2、Mex3培养3h及加入穿心莲内酯0,100,200mg·L^-1再培养6h的MexB基因表达量。采用Mueller-Hinton倍比稀释法,检测头孢他啶、头孢匹罗、氯霉素、左氧氟沙星、卡那霉素、依米配能、美罗培南对上述菌株的最小抑菌浓度(MIC)。结果:培养9h与3h相比,PAO1、Mex1、Mex2、Mex3的MexB表达量显著升高,P值分别为0.031,0.027,0.030,0.012。穿心莲内酯100,200mg·L^-1组与对照组相比,头孢他啶、头孢匹罗、左氧氟沙星、美罗培南对PAO1、Mex1、Mex2、Mex3株菌的MIC分别降低50%,75%,75%和50%~75%,而对PA01株QS信号分子C4-HSL的分泌差异无显著性。结论:外排泵MexAB-OprM主要在稳定生长期表达,穿心莲内酯对铜绿假单胞菌外排泵MexAB-OprM转录表达的抑制作用使其可恢复部分抗菌药物的敏感性,而这种作用并非通过抑制C4-HSL的分泌而实现。

英文摘要:

OBJECTIVE To investigate the effect and mechanism of andrographolide on inhibiting MexAB-OprM efflux pump of Pseudomonas aeruginosa. METHODS The MexB mRNA expressions of PAO1 and MexAB-OprM overexpressing strain (Mexl, Mex2, Mex3) were measured by using real time PCR at 3 h and 9 h after inoculation. In presence of 0,100,200 mg·L^-1 andrographolide, the minimal inhibitory concentration(MIC) of CAZ, CPR, CP, L-OFLX, KM, IPM, MER to those strains was detected by using Mueller-Hinton broth dilution. The effect of andrographolide on quorum sensing signal C4- HSL in PAO1 strain was also determined by a sensor strain. RESULTS The relative MexB mRNA amount of PAO1 and Mex1 ,Mex2,Mex3 cultured for 9 h was significantly higher than those strains cultured for 3 h and P value was 0. 031,0. 027,0. 030,0. 012 sepa rarely. In contrast, the MIC of CAZ,CPR,L-OFLX, MER to those strains in the concentration of 100,200 mg·L^-1 andrographolide also decreased 50%, 75%,75% and 50%-75%, respectively, compared with the control. In addition, no significant difference was observed in the level of C4-HSL secretion in PAO1 strain treated with andrographoiide.. CONCLUSION Mex AB-OprM efflux pump was mainly transcribed in stationary growth phases. The effect of andrograpbolide on inhibiting the transcriptional expression of MexAP-OprM might contribute to recover several antibiotics susceptibility in Pseudomonas aeruginosa. However, this effect should not depend on inhibition of C4-HSL secretion.

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期刊信息
  • 《中国医院药学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中国药学会
  • 主编:陈华庭
  • 地址:武汉市汉口胜利街155号
  • 邮编:430014
  • 邮箱:pharmacy@vip.163.com
  • 电话:027-82836596
  • 国际标准刊号:ISSN:1001-5213
  • 国内统一刊号:ISSN:42-1204/R
  • 邮发代号:38-50
  • 获奖情况:
  • 曾获中国药学会优秀期刊二等奖,中国科协优秀期刊三等奖,湖北省优秀期刊奖
  • 国内外数据库收录:
  • 美国国际药学文摘,美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:53772