首页> 外文期刊>American Journal of Physiology >Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure.
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Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure.

机译:组织因子-X因子结合的阻滞减弱败血症诱导的呼吸和肾衰竭。

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摘要

Tissue factor expression in sepsis activates coagulation in the lung, which potentiates inflammation and leads to fibrin deposition. We hypothesized that blockade of factor X binding to the tissue factor-factor VIIa complex would prevent sepsis-induced damage to the lungs and other organs. Acute lung injury was produced in 15 adult baboons primed with killed Escherichia coli [1 x 10(9) colony-forming units (CFU)/kg], and then 12 h later, they were given 1 x 10(10) CFU/kg live E. coli by infusion. Two hours after live E. coli, animals received antibiotics with or without monoclonal antibody to tissue factor intravenously to block tissue factor-factor X binding. The animals were monitored physiologically for 34 h before being killed and their tissue harvested. The antibody treatment attenuated abnormalities in gas exchange and lung compliance, preserved renal function, and prevented tissue neutrophil influx and bowel edema relative to antibiotics alone (all P < 0.05). It also attenuated fibrinogen depletion (P < 0.01) and decreased proinflammatory cytokines, e.g., IL-6 and -8 (P < 0.01), in systemic and alveolar compartments. Similar protective effects of the antibody on IL-6 and -8 expression and permeability were found in lipopolysaccharide-stimulated endothelial cells. Blockade of factor X binding to the tissue factor-factor VIIa complex attenuates lung and organ injuries in established E. coli sepsis by attenuating the neutrophilic response and inflammatory pathways.
机译:脓毒症中的组织因子表达激活肺中的凝血,从而增强炎症并导致纤维蛋白沉积。我们假设阻断因子X与组织因子VIIa复合物的结合将阻止败血症对肺和其他器官的损害。急性肺损伤是在15只成年狒狒中引发的,它们被杀死的大肠埃希菌[1 x 10(9)集落形成单位(CFU)/ kg]引发,然后在12小时后给予1 x 10(10)CFU / kg通过输注活大肠杆菌。活大肠杆菌后两小时,动物静脉内接受含或不含针对组织因子的单克隆抗体的抗生素,以阻断组织因子X的结合。在处死动物并收集其组织之前,对其进行生理监测34小时。与单独使用抗生素相比,抗体治​​疗可减轻气体交换和肺顺应性异常,保留肾功能,并防止组织中性粒细胞大量涌入和肠水肿(所有P <0.05)。它也减轻了全身和肺泡区室中的纤维蛋白原消耗(P <0.01)并降低了促炎细胞因子,例如IL-6和-8(P <0.01)。在脂多糖刺激的内皮细胞中发现了抗体对IL-6和-8表达和通透性的类似保护作用。阻断X因子与组织因子VIIa复合物的结合,通过减弱嗜中性细胞反应和炎症途径,减轻了已建立的大肠杆菌败血症对肺和器官的伤害。

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