A single dose of endotoxin increases intestinal permeability in healthy humans.

A single dose of endotoxin increases intestinal permeability in healthy humans.
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DOI:
10.1001/archsurg.1988.01400360029003
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发表时间:
1988-12
影响因子:
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通讯作者:
S. O'dwyer;H. R. Michie;T. Ziegler;A. Revhaug;R. Smith;D. Wilmore
S. O'dwyer;H. R. Michie;T. Ziegler;A. Revhaug;R. Smith;D. Wilmore
中科院分区:
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文献类型:
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作者:
S. O'dwyer;H. R. Michie;T. Ziegler;A. Revhaug;R. Smith;D. Wilmore

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为了研究内毒素对肠道屏障功能的影响,我们对接受静脉注射大肠杆菌内毒素 (4 ng/kg) 或 0.9% 盐水溶液的健康人 (N = 12) 的肠道通透性进行了配对研究。在测试注射前 30 分钟和测试注射后 120 分钟,口服两种不可代谢的糖,乳果糖和甘露醇,它们是标准渗透性标记物。施用内毒素/盐溶液后12小时这些物质的尿排泄用于定量肠道通透性。施用内毒素后,乳果糖的全身吸收和排泄几乎增加两倍(平均值+/-SEM,每12小时263+/-36μmol,而盐水研究期间每12小时145+/-19μmol)。注射内毒素后,甘露醇吸收和排泄发生类似但不太明显的变化(每 12 小时 5.7 +/- 0.3 mmol,每 12 小时 4.9 +/- 0.3 mmol)。当给予内毒素后个体12小时乳果糖排泄与全身反应的程度相关时,乳果糖排泄与去甲肾上腺素的产生之间以及乳果糖排泄与最低白细胞计数之间发生显着关系。这些数据表明,短暂接触循环内毒素会增加正常肠道的通透性。这些观察结果与以下假设一致:在危重疾病期间,长期或反复接触全身内毒素或相关细胞因子可能会显着损害胃肠粘膜屏障的完整性。
To investigate the effects of endotoxin on gut barrier function, we performed paired studies of intestinal permeability in healthy humans (N = 12) receiving intravenous Escherichia coli endotoxin (4 ng/kg) or 0.9% saline solution. Two nonmetabolizable sugars, lactulose and mannitol, which are standard permeability markers, were administered orally, 30 minutes before and 120 minutes after the test injection. The 12-hour urinary excretion of these substances after endotoxin/saline solution administration was used to quantitate intestinal permeability. After endotoxin administration systemic absorption and excretion of lactulose increased almost two-fold (mean +/- SEM, 263 +/- 36 mumol per 12 hours vs 145 +/- 19 mumol per 12 hours during saline studies). Similar but less marked alterations in mannitol absorption and excretion occurred after endotoxin injection (5.7 +/- 0.3 mmol per 12 hours vs 4.9 +/- 0.3 mmol per 12 hours). When individual 12-hour lactulose excretion after endotoxin administration was related to the magnitude of systemic responses, a significant relationship occurred between lactulose excretion and elaboration of norepinephrine and between lactulose excretion and minimum white blood cell count. These data suggest that a brief exposure to circulating endotoxin increases the permeability of the normal gut. These observations are consistent with the hypothesis that during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.