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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 peptide α4-short peptide combats Pseudomonas aeruginosa in vitro

  • 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,8 μmol/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,8 μmol/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。

     

    Abstract:
    Objective To explore the effect of a novel antimicrobial peptide α4-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 of α4-short peptide on the growth inhibition curve and biofilm formation of Pseudomonas aeruginosa standard strain (PAO1) was observed in vitro. And the effect of α4-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 of α4-short peptide on their growth curves in vitro.
    Results The proliferation and biofilm formation of PAO1 were inhibited by α4-short peptide, and the best effect was found at 8 μmol/L of α4-short (P < 0.001). IL-6 and TNF-α mRNA relative expression induced by PAO1 in RAW264.7 cells were downregulated by α4-short peptide pretreatment, and the best concentration was 8 μmol/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 by α4-short peptide.
    Conclusions α4-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.

     

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