环丙沙星与乳铁蛋白多肽嵌合体联用对铜绿假单胞菌生物膜及密度感知系统信号分子生成的抑制作用  

Inhibitory Effect of Ciprofloxacin Combined with Lactoferrin- derived Peptides Chimera on the Biofilm Formation and Production of the Signal Molecules of Quorum Sensing System in Pseudomonas aeruginosa

作　　者：左鹏[1] 王爱利[1] 王正云[1] 徐国鹏[1] 胡琼洁[1] 邵冰[1] 徐西琳[1] 熊维宁[1] 熊盛道[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院呼吸与危重症医学科,武汉430030

出　　处：《医药导报》2015年第1期35-39,共5页Herald of Medicine

基　　金：国家自然科学基金资助项目(30770946);中国呼吸道感染优化治疗协作组(CROTC)科研专项基金资助项目(2009042);国家"十二五"支撑课题(2012BAI05B01)

摘　　要：目的比较环丙沙星(CIP)、乳铁蛋白多肽嵌合体(LFchimera)单用及二者联用对铜绿假单胞菌生物膜及密度感知(QS)系统信号分子(AHL)生成的抑制作用。方法以铜绿假单胞菌野生菌株PAO1为实验菌株,分为对照组(未干预的铜绿假单胞菌野生菌株PAO1)、CIP(0.04μg·m L-1)组、LFchimera(0.25μmol·L-1)组、LFchimera(1.00μmol·L-1)组、CIP(0.04μg·m L-1)+LFchimera(1.00μmol·L-1)组,分别定量测定并比较各组PAO1生物被膜和QS系统信号分子表达。结果与对照组PAO1生物膜定量表达(A590)(1.511 3±0.031 8)及QS系统信号分子表达(A420)(0.502 5±0.028 3)比较,CIP(0.04μg·m L-1)组(1.073 3±0.010 9,0.245 3±0.014 0)、LFchimera(0.25μmol·L-1)组(1.065 5±0.011 4,0.235 9±0.010 7)、LFchimera(1.00μmol·L-1)组(0.665 3±0.012 9,0.108 6±0.007 0)和CIP(0.04μg·m L-1)+LFchimera(1.00μmol·L-1)组(0.122 1±0.013 0,0.048 2±0.005 4)均下降(均P<0.05);CIP(0.04μg·m L-1)组和LFchimera(0.25μmol·L-1)组比较,PAO1生物膜定量表达和QS系统信号分子表达差异无统计学意义(P>0.05);LFchimera(1.00μmol·L-1)组PAO1的生物膜定量表达和QS系统信号分子表达较LFchimera(0.25μmol·L-1)组和CIP(0.04μg·m L-1)组均降低(均P<0.05);CIP(0.04μg·m L-1)+LFchimera(1.00μmol·L-1)组和各单独用药组比较,PAO1生物膜的定量表达和QS系统信号分子表达均下降(均P<0.05)。结论亚抑菌浓度的CIP和LFchimera都对铜绿假单胞菌生物膜的形成和QS系统信号分子的生成有抑制作用,且提高LFchimera浓度可加强抑制作用;CIP与LFchimera联用能增强抑制作用,这种作用可能是通过抑制QS系统信号分子的生成实现。Objective To compare the inhibitory effect of single use of ciprofloxacin （CIP）, lactoferrin-derived peptides chimera （LFchimera） and combination of CIP plus LFchimera on the biofilm formation and production of the signal molecules of quorum senging（QS） system in Pseudomonas aeruginosa. Methods The wild type strain of P. aeruginosa-PA01 was used as test strain ,which was divided into the control group , CIP（0.04 μg · mL^-1） group, LFchimera（ 0. 25 μmol · L^-1 and 1.. 00 μmol · L^-1 ） , CIP （ 0.04μg · mL^-1 ） plus LFchimera （ 1.00 μmol · L^-1 ） one. The expression of biofilm and the signal molecules of QS in PAO1 were quantitatively determined respectively, and were compared among groups. Results Compared with those in the control group （1.511 3±0.031 8,0. 502 5 ·0. 028 3 ）, the quantitative expression of biofilm and the signal molecules of QS in CIP group（ 1. 073 3±0. 010 9,0.245 3±0. 0140）, LFchimera low＇d0se group（ 1.0655±0.011 4,0. 235 9±0.010 7 ）, LFchimera high dose group （ 0. 665 3±0. 012 9,0. 108 6 ±. 007 0 ） and the combination group （ 0. 122 1 ± 0. 013 0, 0. 048 2±0. 005 4）were all significantly reduced （P〈0.05）. The quantitative expression of biofilm and the signal molecules of QS had no significant differences between the CIP group and LFchimera low dose group（ P〉0.05 ）, were significantly lower in the LFelaimera high doesgroup compared to the LFchimera low dose group and the CIP group（ P〈0.05 ）, and were remarkably lower in the combination group compared to single drug groups （ P〈0.05 ）. Conclusion Both of CIP and LFehimera at sub-MICs could inhibit biofilm formation and the production of signal molecules of QS in Pseudomonas aeruginosa. The inhibition effect of LFchimera is dose-dependent. This inhibitory effect could be further enhanced when CIP is. combined with LFchimera, which indicats they have synergistic effect on the resistance of biofilm formation in Pseudomonas aeruginosa by suppressing the product

关 键 词：环丙沙星 乳铁蛋白 铜绿假单胞菌 生物膜 密度感知系统 

分 类 号：R969[医药卫生—药理学] R965[医药卫生—药学]