Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats
Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats
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DOI：
10.1136/gut.52.6.874
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发表时间：
2003-06-01
期刊：
影响因子：
24.5
通讯作者：
Scalise, G
中科院分区：
文献类型：
--
作者：
Giacometti, A;Cirioni, O;Scalise, G
背景资料：梗阻性黄疸患者的术后发病率仍然很高，因为对内毒素和炎症级联反应的敏感性增加。目的：设计一项实验研究，以研究保护素肽IB-367（一种带正电荷的抗菌肽）在胆管结扎大鼠中中和大肠杆菌O 111：B4脂多糖（LPS）的功效。方法：成年雄性Wistar大鼠于假手术或胆管结扎（BDL）后1周腹腔注射2 mg/kg大肠杆菌O 111：B4 LPS。研究了六组：安慰剂组、120 mg/kg他唑巴坦-哌拉西林（TZP）组、1 mg/kg IB-367组、安慰剂组、120 mg/kg TZP组和1 mg/kg IB-367组。结果：主要观察指标为：血浆中内毒素和肿瘤坏死因子α（TNF-α）浓度、血液和腹膜中细菌移位的证据以及致死率。LPS后，BDL大鼠的TNF-α血浆水平显著高于假手术动物。与安慰剂和TZP治疗组相比，IB-367导致血浆内毒素和TNF-α浓度显著降低。相比之下，与盐水处理相比，TZP和IB-367均显著减少细菌生长。结论：IB-367具有抗菌和抗内毒素双重作用，可能是一种有效的抑制梗阻性黄疸细菌移位和内毒素释放的药物。
Background: Postoperative morbidity in patients with obstructive jaundice remains high because of increased susceptibility to endotoxin and the inflammatory cascade.Aims: An experimental study was designed to investigate the efficacy of protegrin peptide IB-367, an antimicrobial positively charged peptide, in neutralising Escherichia coli O111:B4 lipopolysaccharide (LPS) in bile duct ligated rats.Methods: Adult male Wistar rats were injected intraperitoneally with 2 mg/kg E coli O111: B4 LPS one week after sham operation or bile duct ligation (BDL). Six groups were studied: sham with placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg IB-367, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1 mg/kg IB-367.Results: Main outcome measures were: endotoxin and tumour necrosis factor alpha (TNF-alpha) concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. After LPS, TNF-alpha plasma levels were significantly higher in BDL rats compared with sham operated animals. IB-367 caused a significant reduction in plasma endotoxin and TNF-alpha concentrations compared with placebo and TZP treated groups. In contrast, both TZP and IB-367 significantly reduced bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo and TZP treated rats and no lethality in sham operated rats, while only IB-367 significantly reduced lethality to 10%.Conclusions: By virtue of its dual antimicrobial and antiendotoxin properties, IB-367 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.