the anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model a prospective randomized study合成抗菌肽的抗炎效果19 - 2.5在一项前瞻性随机研究小鼠脓毒症模型.pdf

Schuerholz et al. Critical Care 2013, 17:R3 /content/17/1/R3 RESEARCH Open Access The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: a prospective randomized study 1*† 1† 2 1 1 3 Tobias Schuerholz , Sabine Doemming , Mathias Hornef , Lukas Martin , Tim-Philipp Simon , Lena Heinbockel , Klaus Brandenburg3 and Gernot Marx1 Abstract Introduction: Increasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti- lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model. Methods: A randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior