Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents
Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents
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DOI：
10.2353/ajpath.2006.050617
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发表时间：
2006-04-01
影响因子：
6
通讯作者：
Fioramonti, J
中科院分区：
文献类型：
--
作者：
Ferrier, L;Bérard, F;Fioramonti, J
大量饮酒者的酒精肝毒性与血液中高内毒素水平和肠通透性增加有关。由于内毒素可以穿过受损的粘膜，我们研究了乙醇损害急性酒精摄入大鼠结肠上皮的机制。摄入3.0 g/kg乙醇后24小时，结肠对Cr-51-乙二胺四乙酸的渗透性增加（3.2 +/- 0.2% vs 2.2 +/- 0.2%），并与显著的内毒素血症相关。抗生素和doxantrazole（肥大细胞膜稳定剂）显著抑制乙醇的作用。摄入后两小时，酒精治疗组大鼠的血浆乙醇浓度是对照组的两倍（155.8 +/- 9.3 mg/dl vs 75.7 +/- 7.6 mg/dl，P < 0.001）。乙醇摄入后，乙醛的管腔浓度显著增加（132.6 +/- 31.6 μ mol/L对20.8 +/- 1.4 μ mol/L，P < 0.05），抗生素减少了这种增加（86.2 +/- 10.9 μ mol/L）。在安装在Ussing室中的结肠样品中，乙醛而不是乙醇使葡聚糖穿过粘膜的通量增加了54%。多桑曲唑可抑制乙醛的作用。这项研究表明，急性和中度的乙醇摄入量改变了上皮屏障，通过乙醇氧化成乙醛的结肠微生物。和下游肥大细胞活化。这种改变保持较长时间可能会导致过量的内毒素通过，这可以解释酒精性肝病患者中经常观察到的内毒素血症。
Alcohol hepatic toxicity in heavy drinkers is associated with high endotoxin blood levels and increased intestinal permeability. Because endotoxins can cross damaged mucosa, we investigated the mechanisms through which ethanol impairs the colonic epithelium of rats submitted to acute alcohol intake. Colonic permeability to Cr-51-ethylenediamintetraacetic acid was increased 24 hours after 3.0 g/kg ethanol intake (3.2 +/- 0.2% versus 2.2 +/- 0.2%) and was associated with significant endotoxemia. Antibiotics and doxantrazole (a Mast cell membrane stabilizer) significantly inhibited the effect of ethanol. Two hours after intake, plasma concentrations of ethanol were twofold higher in antibiotic-treated rats than in controls (155.8 +/- 9.3 mg/dl versus 75.7 +/- 7.6 mg/dl, P < 0.001). Lumenal concentrations of acetaldehyde were markedly increased after ethanol intake (132.6 +/- 31.6 mu mol/L versus 20.8 +/- 1.4 mu mol/L, P < 0.05) and antibiotics diminished this increase (86.2 +/- 10.9 mu mol/L). in colonic samples mounted in Ussing chambers, acetaklehyde but not ethanol increased dextran flux across the mucosa by 54%. Doxantrazole inhibited the effect of acetaklehyde. This study demonstrates that an acute and moderate ethanol intake alters the epithelial barrier through ethanol oxidation into acetaklehyde by the colonic microflora. and downstream mast cell activation. Such alterations that remain for longer periods could result in excessive endotoxin passage, which could explain the subsequent endotoxemia frequently observed in patients with alcoholic liver disease.