Small bowel protection against NSAID-injury in rats: Effect of rifaximin, a poorly absorbed, GI targeted, antibiotic
Small bowel protection against NSAID-injury in rats: Effect of rifaximin, a poorly absorbed, GI targeted, antibiotic
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DOI：
10.1016/j.phrs.2015.12.031
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发表时间：
2016-02-01
影响因子：
9.3
通讯作者：
Scarpignato, Carmelo
中科院分区：
文献类型：
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作者：
Fornai, Matteo;Antonioli, Luca;Scarpignato, Carmelo
非甾体类抗炎药除了对上消化道产生有害影响外，还会损害小肠和大肠。虽然潜在的机制尚不清楚，但有证据表明肠道细菌起着关键作用。本研究检查了利福昔明-EIR（R-EIR，50 mg/kg BID，i.g.）的延迟释放制剂的肠保护作用，在吲哚美辛（IND，1.5 mg/kg BID，持续14天）给药诱导的肠病大鼠模型中，一种具有广谱抗菌活性的吸收不良抗生素。R-EIR在IND给药前7天开始给药或与IND给药同时给药。在治疗结束时，采集血样以评价血红蛋白（Hb）浓度（作为消化道出血的指标）。处理小肠用于：（1）肠损伤的组织学评估（病变长度占检查总长度的百分比）;（2）组织髓过氧化物酶（MPO）和TNF水平的测定，作为炎症标志物;（3）组织丙二醛（MDA）和蛋白质羰基浓度的测定，分别作为脂质和蛋白质过氧化的指标;（4）主要细菌门的评价。IND显著降低Hb水平，该作用被R-EIR显著减弱，IND还诱导空肠和回肠病变的发生。在这两个肠道区域，R-EIR显着降低病变的百分比，与接受IND的大鼠相比。IND处理组大鼠空肠和回肠的炎症和组织过氧化反应标志物均显著增加。然而，在用R-EIR处理的大鼠中，这些参数与对照组中观察到的参数没有显著差异。R-EIR还能够抵消由INDO诱导的变形菌门和厚壁菌门丰度的增加。总之，R-EIR治疗可显著预防IND诱导的肠道损伤，这种肠道保护作用与组织炎症、氧化应激和消化道出血的减少以及NSAID诱导的细菌群改变的逆转相关。(C)2015爱思唯尔有限公司版权所有。
Nonsteroidal anti-inflammatory drugs, besides exerting detrimental effects on the upper digestive tract, can also damage the small and large intestine. Although the underlying mechanisms remain unclear, there is evidence that enteric bacteria play a pivotal role. The present study examined the enteroprotective effects of a delayed-release formulation of rifaximin-EIR (R-EIR, 50 mg/kg BID, i.g.), a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, in a rat model of enteropathy induced by indomethacin (IND, 1.5 mg/kg BID for 14 days) administration. R-EIR was administered starting 7 days before or in concomitance with IND administration. At the end of treatments, blood samples were collected to evaluate hemoglobin (Hb) concentration (as an index of digestive bleeding). Small intestine was processed for: (1) histological assessment of intestinal damage (percentage length of lesions over the total length examined); (2) assay of tissue myeloperoxidase (MPO) and TNF levels, as markers of inflammation; (3) assay of tissue malondialdehyde (MDA) and protein carbonyl concentrations, as an index of lipid and protein peroxidation, respectively; (4) evaluation of the major bacterial phyla. IND significantly decreased Hb levels, this effect being significantly blunted by R-EIR IND also induced the occurrence of lesions in the jejunum and ileum. In both intestinal regions, R-EIR significantly reduced the percentage of lesions, as compared with rats receiving IND alone. Either the markers of inflammation and tissue peroxidation were significantly increased in jejunum and ileum from IND-treated rats. However, in rats treated with R-EIR, these parameters were not significantly different from those observed in controls. R-EIR was also able to counterbalance the increase in Proteobacteria and Firmicutes abundance induced by INDO. To summarize, R-EIR treatment significantly prevents IND-induced intestinal damage, this enteroprotective effect being associated with a decrease in tissue inflammation, oxidative stress and digestive bleeding as well as reversal of NSAID-induced alterations in bacterial population. (C) 2015 Elsevier Ltd. All rights reserved.