Department for Clinical and Molecular Microbiology, Clinical Hospital Center, Zagreb, Croatia.
Dig Dis Sci. 2010 Aug;55(8):2211-8. doi: 10.1007/s10620-009-1034-7. Epub 2009 Nov 19.
The aim of this study was to investigate the effect of the macrolide antibiotic azithromycin on mucosal changes and colonic bacterial load in a murine model of colitis.
Colitis was induced in CD1 mice using enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. Four experimental groups of animals (N = 10 per group) were treated with 50 mg/kg/day azithromycin (AZ) or metronidazole (MN) perorally, starting 24 h before (AZ-1, MN-1) or 6 h after (AZ+1, MN+1) induction of colitis and for consecutive 5 days. Additional experimental mice group was treated with 10 mg/kg/day methylprednisolone intraperitoneally after induction of experimental colitis in the same manner (MP). Two control groups consisted of healthy animals (C) that received the challenge enema with phosphate-buffered saline (PBS) and animals with experimental colitis (chall) treated with equivolume of PBS perorally. Clinical score (0-5) and histopathologic score (0-30) were used to assess inflammatory changes, and colon washings were used to determine changes in bacterial load.
The anti-inflammatory effect of azithromycin did not differ from the effect of methylprednisolone, when compared with control group with experimental colitis. Metronidazole did not show a significant anti-inflammatory effect. Number of colonic bacteria did not differ significantly between control and experimental groups of animals.
We documented the anti-inflammatory effect of azithromycin in a murine model of acute colitis, suggesting that effects were targeted to oxidative burst and on mucosal/bacterial interface, independent of luminal bacterial load. Further studies should be focused on effect of azithromycin on the role of bacterial biofilm in perpetuation of chronic intestinal inflammation.
本研究旨在探讨大环内酯类抗生素阿奇霉素对结肠炎模型中黏膜变化和结肠细菌负荷的影响。
采用直肠给予 0.2%二硝基氟苯溶液联合皮肤致敏的方法诱导 CD1 小鼠结肠炎。将 4 组实验动物(每组 10 只)分别用 50mg/kg/天阿奇霉素(AZ)或甲硝唑(MN)经口给药,在结肠炎诱导前 24 小时(AZ-1、MN-1)或诱导后 6 小时(AZ+1、MN+1)开始连续 5 天给药。另外一组实验小鼠在以同样的方式诱导实验性结肠炎后用 10mg/kg/天甲基强的松龙腹腔内给药(MP)。两个对照组由接受磷酸盐缓冲盐水(PBS)直肠挑战的健康动物(C)和接受等容量 PBS 经口给药的实验性结肠炎动物(chall)组成。临床评分(0-5)和组织病理学评分(0-30)用于评估炎症变化,结肠冲洗液用于确定细菌负荷变化。
与实验性结肠炎对照组相比,阿奇霉素的抗炎作用与甲基强的松龙的作用无差异。甲硝唑没有显示出明显的抗炎作用。结肠细菌数量在对照组和实验组动物之间没有显著差异。
我们在急性结肠炎的小鼠模型中记录了阿奇霉素的抗炎作用,表明其作用靶向于氧化爆发和黏膜/细菌界面,与腔内容物细菌负荷无关。进一步的研究应集中在阿奇霉素对细菌生物膜在慢性肠道炎症持续存在中的作用的影响上。