环丙沙星联合乳铁蛋白多肽嵌合体对铜绿假单胞菌毒力因子的影响  

Effect of Ciprofloxacin Combined with Lactoferrin-derived Peptides Chimera on Virulence Factors of Pseudomonas aeruginosa

作　　者：左鹏[1] 王正云[1] 徐国鹏[1,2] 胡琼洁[3] 邵冰[4] 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,卫生部呼吸系疾病重点实验室,武汉430030 [2]南京医科大学附属苏州医院呼吸内科,苏州215002 [3]华中科技大学同济医学院附属同济医院放射科,武汉430030 [4]华中科技大学同济医学院护理学系,武汉430030

出　　处：《华中科技大学学报（医学版）》2013年第4期446-450,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30770946!);中国呼吸道感染优化治疗协作组(CROTC)科研专项基金项目(No.2009042);国家"十二五"支撑课题项目(No.2012BAI05B01)

摘　　要：目的研究环丙沙星(CIP)、乳铁蛋白多肽嵌合体(LFchimera)单用及二者联合对铜绿假单胞菌毒力因子生成的影响。方法以铜绿假单胞菌野生菌株PAO1为实验菌株,分为对照组(无任何干预的铜绿假单胞菌野生菌株PAO1),CIP(0.04μg/mL)组,LFchimera(0.25μmol/L)组,LFchimera(1μmol/L)组,CIP(0.04μg/mL)+LFchimera(1μmol/L)组,分别测定毒力因子绿脓菌素的浓度(氯仿萃取法)、弹性蛋白酶(弹性蛋白-刚果红法)、胞外蛋白水解酶(偶氮酪蛋白法)。结果和对照组比较,CIP组,LFchimera(0.25μmol/L)组,LFchimera(1μmol/L)组,CIP(0.04μg/mL)联合LFchimera(1μmol/L)组的绿脓菌素浓度下降,弹性蛋白酶和蛋白水解酶活性降低,差异均有统计学意义(均P<0.05);CIP组和LFchimera(0.25μmol/L)组比较,绿脓菌素浓度、弹性蛋白酶和蛋白水解酶活性的差异均无统计学意义(均P>0.05);LFchimera(1μmol/L)组绿脓菌素浓度、弹性蛋白酶和蛋白水解酶活性较CIP组和LFchimera(0.25μmol/L)组降低,差异均有统计学意义(均P<0.05);CIP(0.04μg/mL)联合LFchimera(1μmol/L)组和各单独用药组比较,绿脓菌素浓度下降,弹性蛋白酶和蛋白水解酶活性降低,差异均有统计学意义(均P<0.05)。结论亚抑菌浓度的CIP和LFchimera都对铜绿假单胞菌毒力因子(绿脓菌素、弹性蛋白酶和蛋白水解酶)的生成有抑制作用,随着LFchime-ra浓度的提高这种抑制作用加强,而CIP联合LFchimera能进一步增强这种抑制作用,说明两者在抗铜绿假单胞菌毒力因子方面有协同作用。Objective To investigate the effect of ciprofloxacin（CIP）in combination with lactoferrin-derived peptides chimera（LFchimera）on virulence factors of Pseudomonas aeruginosa（P.aeruginosa）.Methods The wild type strain of P.aeruginosa-PAO1was used as experimental strain.Five groups were established,including control group（the wild type strain of P.aeruginosa-PAO1without any intervention）,CIP group（0.04μg/mL）group,LFchimera（0.25and 1μmol/L） groups,LFchimera（1μmol/L）plus CIP（0.04μg/mL）group.The virulence factors,including pyocyanin,elastase and extracellular proteolytic enzyme,were determined by chloroform extraction method,Elastin-Congo Red method and Azocasein method,respectively.Results The pyocyanin concentration,elastase activity and proteolytic enzyme activity were significantly reduced in the CIP group,0.25μmol/L LFchimera group,1μmol/L LFchimera group and CIP plus LFchimera group compared with those in the control group（P〈0.05）.There was no significant difference in the virulence factors between the CIP group and the 0.25μmol/L LFchimera group（P〈0.05）.Moreover,the level of the virulence factors was substantially reduced in the CIP plus LFchimera group when compared with 1μmol/L LFchimera group and CIP group（P〉0.05）.Conclusion Both CIP and LFchimera at sub-MICs can inhibit the production of virulence factors（such as pyocyanine,elastase and proteolytic enzyme）in Pseudomonas aeruginosa.They have synergistic effect on the resistance of virulence factors in Pseudomonas aeruginosa.

关 键 词：铜绿假单胞菌 环丙沙星 乳铁蛋白 多肽 毒力因子 

分 类 号：R453.2[医药卫生—治疗学]