新型抗菌肽α4-短肽体外对铜绿假单胞菌的抑制作用  

A novel antimicrobial peptideα4-short peptide combats Pseudomonas aeruginosa in vitro

作　　者：宋娟 张宇晔 陈翠翠[1,3] 王林林 童琳[1,3] 宋元林[1,2,3] SONG Juan;ZHANG Yu-ye;CHEN Cui-cui;WANG Lin-lin;TONG Lin;SONG Yuan-lin(Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Institute of Major Infectious Diseases and Biosafety,Shanghai 200032,China;Shanghai Key Laboratory of Lung Inflammation and Injury,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院呼吸与危重症医学科,上海200032 [2]上海市重大传染病与生物安全研究院,上海200032 [3]上海市肺部炎症与损伤重点实验室,上海200032

出　　处：《中国临床医学》2023年第1期80-84,共5页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金(82130001,82170088);上海市市级科技重大专项(ZD2021CY001);上海市肺部炎症与损伤重点实验室(20DZ2261200)。

摘　　要：目的探讨抗菌肽α4-短肽体外对铜绿假单胞菌生长的抑制作用,为临床治疗以铜绿假单胞菌为主的肺部感染性疾病提供新思路。方法体外观察α4-短肽对铜绿假单胞菌标准株PAO1体外生长曲线和生物膜形成的影响,并分析α4-短肽对PAO1刺激后巨噬细胞(RAW264.7)炎症水平的影响。选取若干株临床耐药菌株,体外观察α4-短肽对其生长曲线的影响。结果α4-短肽可抑制PAO1生长及生物膜的形成,8μmol/L时效果达最佳(P<0.001)。α4-短肽预处理RAW264.7后,由PAO1引起的IL-6和TNF-α的mRNA表达下调,8μmol/L时效果最佳(P<0.001)。分离得到4株铜绿假单胞菌多重耐药菌株和2株肺炎克雷伯菌耐药菌,α4-短肽对其生长均产生较好的抑制作用。结论α4-短肽能较好地抑制铜绿假单胞菌生长及其生物膜形成,降低铜绿假单胞菌导致的炎症水平,并对临床耐药菌株有较好的抑制效果。Objective To explore the effect of a novel antimicrobial peptideα4-short peptide on the growth inhibition of Pseudomonas aeruginosa,in order to provide a new thought for clinical treatment of pulmonary infectious diseases.Methods The effect ofα4-short peptide on the growth inhibition curve and biofilm formation of Pseudomonas aeruginosa standard strain(PAO1)was observed in vitro.And the effect ofα4-short peptide on the inflammatory level of RAW264.7 cells stimulated by PAO1 was analyzed.Several clinical resistant strains were isolated to observe the effect ofα4-short peptide on their growth curves in vitro.Results The proliferation and biofilm formation of PAO1 were inhibited byα4-short peptide,and the best effect was found at 8μmol/L ofα4-short(P<0.001).IL-6 and TNF-αmRNA relative expression induced by PAO1 in RAW264.7 cells were downregulated byα4-short peptide pretreatment,and the best concentration was 8μmol/L(P<0.001).The proliferation of four isolated multidrug-resistant strains of Pseudomonas aeruginosa and two isolated drug-resistant strains of Klebsiella pneumoniae were inhibited byα4-short peptide.Conclusionsα4-short peptide could inhibit proliferation and biofilm formation of Pseudomonas aeruginosa as well as reduce inflammatory level in macrophage stimulated by PAO1.It also showed satisfactory inhibitory effect on clinical drug-resistant strains.

关 键 词：铜绿假单胞菌 肺部感染 抗菌肽 短腭、肺和鼻上皮克隆1 α4-短肽 

分 类 号：R563[医药卫生—呼吸系统]