苯丙氨酸-精氨酸-β-萘酰胺对泛耐药铜绿假单胞菌作用的体内外研究  

Research on impact of phenyl-arginine-β-naphthylamide′s on clinical pandrug-resistance psendomonas aeruginosain vitro and in vivo

作　　者：张芸[1] 刘明涛[1] 盛美艳[1] 李玉[1] 

机构地区：[1]山东大学齐鲁医院呼吸科,山东济南250012

出　　处：《中华医院感染学杂志》2011年第11期2164-2167,共4页Chinese Journal of Nosocomiology

基　　金：山东省科技攻关项目(2006GG2202013)

摘　　要：目的研究外排泵抑制剂苯丙氨酸-精氨酸-β-萘酰胺(phenyl-arginine--βnaphthylamide,PAβN)在体外及兔体内对铜绿假单胞菌临床泛耐药菌株的外排泵抑制作用。方法挑选外排泵阳性的临床泛耐药铜绿假单胞菌株为对照组,微量稀释法测定体外使用PAβN前后对12种抗菌药物的MIC值;同时建立兔感染铜绿假单胞菌的组织笼实验模型,随机分为9组,每3组为一大组,注入菌液后分别给予不同的给药方案,取组织液比较铜绿假单胞菌对各种抗菌药物MIC的变化及菌落计数。结果共有3株菌对环丙沙星的MIC在加入羰基氰氯苯腙(CCCP)后下降≥4倍;体外使用PAβN后铜绿假单胞菌对抗菌药物的MIC均有所下降,与对照组比较,差异有统计学意义(t=4.33,P<0.05);其中以喹诺酮类、碳青霉烯类明显;兔体内使用PAβN后没有出现明显的不良反应,用药后3株铜绿假单胞菌对抗菌药物的MIC有不同程度下降,与对照组比较,差异有统计学意义(t=4.23,P<0.05);但是较体外作用弱,差异有统计学意义(t=2.71,P<0.05);单独使用环丙沙星组与联合使用PAβN组菌落计数相比,差异有统计学意义(P<0.05)。结论 PAβN在体外及兔体内都能抑制临床泛耐药铜绿假单胞菌外排泵的表达,可降低MIC,提高效果,但对不同药物的敏感性不同,体内作用比体外明显要弱。OBJECTIVE To study whether efflux pump inhibitors（EPI）phenyl-arginine-β-naphthylamide（PAβN） can inhibit the efflux pump overexpression of clinical pandrug-resistant Pseudomonas aeruginosa in vitro and in vivo.METHODS Totally 3 clinical pandrug-resistant P.aeruginosa which express efflux pump were selected.The minimal inhibitory concentrations（MICs） of 12 antibiotics before and after PAβN used was tested by microdilution method.Tissue cage infection model of clinical pandrug-resistance P.aeruginosa was established in rabbits and then divided into 9 groups by table random digit.They were treated in different ways.Group 1-3 were injected into the tissie cage with PAβN 0.5mg/d for 3 days;group 4-6 were injected with ciprofloxacin by vein;group 7-9 were injected with ciprofloxacin by vein and PAβN into tissue cage at the same time for 3 days.Do colony countings of group 4-9.RESULTS After PAβN used in vitro,MICs of the antibiotics decreased significantly,（t=4.33,P〈0.05）.P.aeruginosa used in animals treated with PAβN showed meaningful decreased MICs too,（t=4.23,P〈0.05）.The colony countings of group used ciprofloxacin and PAβN had satistic diference compared to group used ciprofloxacin alone.CONCLUSION PAβN can inhibit the efflux pump expression of clinical pandrug-resistant P.aeruginosa in vitro and in vivo.It can decrease the MICs of antibiotics,showed different effects to different drugs.The action is weaker in vivo than in vitro.

关 键 词：铜绿假单胞菌 外排泵 抑制剂 苯丙氨酸-精氨酸-β-萘酰胺 

分 类 号：R378.991[医药卫生—病原生物学]