Giacometti Andrea, Cirioni Oscar, Ghiselli Roberto, Mocchegiani Federico, Silvestri Carmela, Orlando Fiorenza, Kamysz Wojciech, Licci Alberto, Kamysz Elzbieta, Lukasiak Jerzy, Saba Vittorio, Scalise Giorgio
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Crit Care Med. 2006 Sep;34(9):2415-20. doi: 10.1097/01.CCM.0000231879.11963.EB.
To investigate the efficacy of amphibian antimicrobial peptides in preventing bacterial translocation and neutralizing endotoxins in bile duct-ligated rats.
Prospective, randomized, controlled animal study.
Research laboratory in a university hospital.
Adult male Wistar rats.
Adult male Wistar rats underwent sham operation or bile duct ligation (BDL). Eight groups were studied: sham operation with saline treatment, sham operation with 120 mg/kg tazobactam-piperacillin, sham operation with 2 mg/kg uperin 3.6, sham operation with 2 mg/kg magainin2, BDL with saline treatment, BDL with 120 mg/kg tazobactam-piperacillin, BDL with 2 mg/kg uperin 3.6, and BDL with 2 mg/kg magainin2.
Main outcome measures were: endotoxin and tumor necrosis factor-alpha concentrations in plasma and evidence of bacterial translocation in blood, peritoneum, liver, and mesenteric lymph nodes. Endotoxin and tumor necrosis factor-alpha plasma levels were significantly higher in BDL rats compared with sham-operated animals. All amphibian peptides achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration when compared with saline- and tazobactam-piperacillin-treated groups. On the other hand, both tazobactam-piperacillin and peptides significantly reduced bacterial growth compared with the control. Tazobactam-piperacillin and magainin2 exerted the maximal inhibition of bacterial growth.
In conclusion, because of their multifunctional properties, amphibian peptides could be interesting compounds to inhibit bacterial translocation and endotoxin release in obstructive jaundice.
研究两栖类抗菌肽在预防胆管结扎大鼠细菌移位及中和内毒素方面的疗效。
前瞻性、随机、对照动物研究。
大学医院的研究实验室。
成年雄性Wistar大鼠。
成年雄性Wistar大鼠接受假手术或胆管结扎(BDL)。研究了八组:生理盐水处理的假手术组、120 mg/kg他唑巴坦-哌拉西林处理的假手术组、2 mg/kg上蛙皮素3.6处理的假手术组、2 mg/kg马盖宁2处理的假手术组、生理盐水处理的BDL组、120 mg/kg他唑巴坦-哌拉西林处理的BDL组、2 mg/kg上蛙皮素3.6处理的BDL组以及2 mg/kg马盖宁2处理的BDL组。
主要观察指标为:血浆中内毒素和肿瘤坏死因子-α浓度以及血液、腹膜、肝脏和肠系膜淋巴结中细菌移位的证据。与假手术动物相比,BDL大鼠的血浆内毒素和肿瘤坏死因子-α水平显著更高。与生理盐水和他唑巴坦-哌拉西林处理组相比,所有两栖类肽均能显著降低血浆内毒素和肿瘤坏死因子-α浓度。另一方面,与对照组相比,他唑巴坦-哌拉西林和肽均能显著减少细菌生长。他唑巴坦-哌拉西林和马盖宁2对细菌生长的抑制作用最大。
总之,由于其多功能特性,两栖类肽可能是抑制梗阻性黄疸中细菌移位和内毒素释放的有趣化合物。